Marine Pharmacology in 2014–2015: Marine Compounds with Antibacterial, Antidiabetic, Antifungal, Anti-Inflammatory, Antiprotozoal, Antituberculosis, Antiviral, and Anthelmintic Activities; Affecting the Immune and Nervous Systems, and Other Miscellaneous Mechanisms of Action
Identifieur interne : 000A57 ( Pmc/Corpus ); précédent : 000A56; suivant : 000A58Marine Pharmacology in 2014–2015: Marine Compounds with Antibacterial, Antidiabetic, Antifungal, Anti-Inflammatory, Antiprotozoal, Antituberculosis, Antiviral, and Anthelmintic Activities; Affecting the Immune and Nervous Systems, and Other Miscellaneous Mechanisms of Action
Auteurs : Alejandro M. S. Mayer ; Aimee J. Guerrero ; Abimael D. Rodríguez ; Orazio Taglialatela-Scafati ; Fumiaki Nakamura ; Nobuhiro FusetaniSource :
- Marine Drugs [ 1660-3397 ] ; 2019.
Abstract
The systematic review of the marine pharmacology literature from 2014 to 2015 was completed in a manner consistent with the 1998–2013 reviews of this series. Research in marine pharmacology during 2014–2015, which was reported by investigators in 43 countries, described novel findings on the preclinical pharmacology of 301 marine compounds. These observations included antibacterial, antifungal, antiprotozoal, antituberculosis, antiviral, and anthelmintic pharmacological activities for 133 marine natural products, 85 marine compounds with antidiabetic, and anti-inflammatory activities, as well as those that affected the immune and nervous system, and 83 marine compounds that displayed miscellaneous mechanisms of action, and may probably contribute to novel pharmacological classes upon further research. Thus, in 2014–2015, the
Url:
DOI: 10.3390/md18010005
PubMed: 31861527
PubMed Central: 7024264
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PMC:7024264Le document en format XML
<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Marine Pharmacology in 2014–2015: Marine Compounds with Antibacterial, Antidiabetic, Antifungal, Anti-Inflammatory, Antiprotozoal, Antituberculosis, Antiviral, and Anthelmintic Activities; Affecting the Immune and Nervous Systems, and Other Miscellaneous Mechanisms of Action</title><author><name sortKey="Mayer, Alejandro M S" sort="Mayer, Alejandro M S" uniqKey="Mayer A" first="Alejandro M. S." last="Mayer">Alejandro M. S. Mayer</name><affiliation><nlm:aff id="af1-marinedrugs-18-00005">Department of Pharmacology, College of Graduate Studies, Midwestern University, 555 31st Street, Downers Grove, IL 60515, USA;<email>aguerrero89@midwestern.edu</email></nlm:aff></affiliation></author><author><name sortKey="Guerrero, Aimee J" sort="Guerrero, Aimee J" uniqKey="Guerrero A" first="Aimee J." last="Guerrero">Aimee J. Guerrero</name><affiliation><nlm:aff id="af1-marinedrugs-18-00005">Department of Pharmacology, College of Graduate Studies, Midwestern University, 555 31st Street, Downers Grove, IL 60515, USA;<email>aguerrero89@midwestern.edu</email></nlm:aff></affiliation></author><author><name sortKey="Rodriguez, Abimael D" sort="Rodriguez, Abimael D" uniqKey="Rodriguez A" first="Abimael D." last="Rodríguez">Abimael D. Rodríguez</name><affiliation><nlm:aff id="af2-marinedrugs-18-00005">Molecular Sciences Research Center, University of Puerto Rico, 1390 Ponce de León Avenue, San Juan, PR 00926, USA;<email>abimael.rodriguez1@upr.edu</email></nlm:aff></affiliation></author><author><name sortKey="Taglialatela Scafati, Orazio" sort="Taglialatela Scafati, Orazio" uniqKey="Taglialatela Scafati O" first="Orazio" last="Taglialatela-Scafati">Orazio Taglialatela-Scafati</name><affiliation><nlm:aff id="af3-marinedrugs-18-00005">Department of Pharmacy, University of Naples “Federico II”, Via D. Montesano 49, I-80131 Napoli, Italy;<email>scatagli@unina.it</email></nlm:aff></affiliation></author><author><name sortKey="Nakamura, Fumiaki" sort="Nakamura, Fumiaki" uniqKey="Nakamura F" first="Fumiaki" last="Nakamura">Fumiaki Nakamura</name><affiliation><nlm:aff id="af4-marinedrugs-18-00005">Department of Chemistry and Biochemistry, Graduate School of Advanced Science and Engineering, Waseda University, 3-4-1 Okubo, Shinjuku-ku, Tokyo 169-8555, Japan;<email>what-will_be.x2@akane.waseda.jp</email></nlm:aff></affiliation></author><author><name sortKey="Fusetani, Nobuhiro" sort="Fusetani, Nobuhiro" uniqKey="Fusetani N" first="Nobuhiro" last="Fusetani">Nobuhiro Fusetani</name><affiliation><nlm:aff id="af5-marinedrugs-18-00005">Fisheries and Oceans Hakodate, Hakodate 041-8611, Japan;<email>anobu@fish.hokudai.ac.jp</email></nlm:aff></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">31861527</idno><idno type="pmc">7024264</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7024264</idno><idno type="RBID">PMC:7024264</idno><idno type="doi">10.3390/md18010005</idno><date when="2019">2019</date><idno type="wicri:Area/Pmc/Corpus">000A57</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000A57</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Marine Pharmacology in 2014–2015: Marine Compounds with Antibacterial, Antidiabetic, Antifungal, Anti-Inflammatory, Antiprotozoal, Antituberculosis, Antiviral, and Anthelmintic Activities; Affecting the Immune and Nervous Systems, and Other Miscellaneous Mechanisms of Action</title><author><name sortKey="Mayer, Alejandro M S" sort="Mayer, Alejandro M S" uniqKey="Mayer A" first="Alejandro M. S." last="Mayer">Alejandro M. S. Mayer</name><affiliation><nlm:aff id="af1-marinedrugs-18-00005">Department of Pharmacology, College of Graduate Studies, Midwestern University, 555 31st Street, Downers Grove, IL 60515, USA;<email>aguerrero89@midwestern.edu</email></nlm:aff></affiliation></author><author><name sortKey="Guerrero, Aimee J" sort="Guerrero, Aimee J" uniqKey="Guerrero A" first="Aimee J." last="Guerrero">Aimee J. Guerrero</name><affiliation><nlm:aff id="af1-marinedrugs-18-00005">Department of Pharmacology, College of Graduate Studies, Midwestern University, 555 31st Street, Downers Grove, IL 60515, USA;<email>aguerrero89@midwestern.edu</email></nlm:aff></affiliation></author><author><name sortKey="Rodriguez, Abimael D" sort="Rodriguez, Abimael D" uniqKey="Rodriguez A" first="Abimael D." last="Rodríguez">Abimael D. Rodríguez</name><affiliation><nlm:aff id="af2-marinedrugs-18-00005">Molecular Sciences Research Center, University of Puerto Rico, 1390 Ponce de León Avenue, San Juan, PR 00926, USA;<email>abimael.rodriguez1@upr.edu</email></nlm:aff></affiliation></author><author><name sortKey="Taglialatela Scafati, Orazio" sort="Taglialatela Scafati, Orazio" uniqKey="Taglialatela Scafati O" first="Orazio" last="Taglialatela-Scafati">Orazio Taglialatela-Scafati</name><affiliation><nlm:aff id="af3-marinedrugs-18-00005">Department of Pharmacy, University of Naples “Federico II”, Via D. Montesano 49, I-80131 Napoli, Italy;<email>scatagli@unina.it</email></nlm:aff></affiliation></author><author><name sortKey="Nakamura, Fumiaki" sort="Nakamura, Fumiaki" uniqKey="Nakamura F" first="Fumiaki" last="Nakamura">Fumiaki Nakamura</name><affiliation><nlm:aff id="af4-marinedrugs-18-00005">Department of Chemistry and Biochemistry, Graduate School of Advanced Science and Engineering, Waseda University, 3-4-1 Okubo, Shinjuku-ku, Tokyo 169-8555, Japan;<email>what-will_be.x2@akane.waseda.jp</email></nlm:aff></affiliation></author><author><name sortKey="Fusetani, Nobuhiro" sort="Fusetani, Nobuhiro" uniqKey="Fusetani N" first="Nobuhiro" last="Fusetani">Nobuhiro Fusetani</name><affiliation><nlm:aff id="af5-marinedrugs-18-00005">Fisheries and Oceans Hakodate, Hakodate 041-8611, Japan;<email>anobu@fish.hokudai.ac.jp</email></nlm:aff></affiliation></author></analytic><series><title level="j">Marine Drugs</title><idno type="eISSN">1660-3397</idno><imprint><date when="2019">2019</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>The systematic review of the marine pharmacology literature from 2014 to 2015 was completed in a manner consistent with the 1998–2013 reviews of this series. Research in marine pharmacology during 2014–2015, which was reported by investigators in 43 countries, described novel findings on the preclinical pharmacology of 301 marine compounds. These observations included antibacterial, antifungal, antiprotozoal, antituberculosis, antiviral, and anthelmintic pharmacological activities for 133 marine natural products, 85 marine compounds with antidiabetic, and anti-inflammatory activities, as well as those that affected the immune and nervous system, and 83 marine compounds that displayed miscellaneous mechanisms of action, and may probably contribute to novel pharmacological classes upon further research. Thus, in 2014–2015, the <italic>preclinical</italic> marine natural product pharmacology pipeline provided novel pharmacology as well as new lead compounds for the <italic>clinical</italic> marine pharmaceutical pipeline, and thus continued to contribute to ongoing global research for alternative therapeutic approaches to many disease categories.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Mayer, A M S" uniqKey="Mayer A">A.M.S. Mayer</name></author><author><name sortKey="Lehmann, V K B" uniqKey="Lehmann V">V.K.B. Lehmann</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Mayer, A M" uniqKey="Mayer A">A.M. Mayer</name></author><author><name sortKey="Hamann, M T" uniqKey="Hamann M">M.T. Hamann</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Mayer, A M S" uniqKey="Mayer A">A.M.S. Mayer</name></author><author><name sortKey="Hamann, M T" uniqKey="Hamann M">M.T. 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<front><journal-meta><journal-id journal-id-type="nlm-ta">Mar Drugs</journal-id><journal-id journal-id-type="iso-abbrev">Mar Drugs</journal-id><journal-id journal-id-type="publisher-id">marinedrugs</journal-id><journal-title-group><journal-title>Marine Drugs</journal-title></journal-title-group><issn pub-type="epub">1660-3397</issn><publisher><publisher-name>MDPI</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">31861527</article-id><article-id pub-id-type="pmc">7024264</article-id><article-id pub-id-type="doi">10.3390/md18010005</article-id><article-id pub-id-type="publisher-id">marinedrugs-18-00005</article-id><article-categories><subj-group subj-group-type="heading"><subject>Review</subject></subj-group></article-categories><title-group><article-title>Marine Pharmacology in 2014–2015: Marine Compounds with Antibacterial, Antidiabetic, Antifungal, Anti-Inflammatory, Antiprotozoal, Antituberculosis, Antiviral, and Anthelmintic Activities; Affecting the Immune and Nervous Systems, and Other Miscellaneous Mechanisms of Action</article-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Mayer</surname><given-names>Alejandro M. S.</given-names></name><xref ref-type="aff" rid="af1-marinedrugs-18-00005">1</xref><xref rid="c1-marinedrugs-18-00005" ref-type="corresp">*</xref></contrib><contrib contrib-type="author"><name><surname>Guerrero</surname><given-names>Aimee J.</given-names></name><xref ref-type="aff" rid="af1-marinedrugs-18-00005">1</xref></contrib><contrib contrib-type="author"><name><surname>Rodríguez</surname><given-names>Abimael D.</given-names></name><xref ref-type="aff" rid="af2-marinedrugs-18-00005">2</xref></contrib><contrib contrib-type="author"><contrib-id contrib-id-type="orcid" authenticated="true">https://orcid.org/0000-0001-8010-0180</contrib-id><name><surname>Taglialatela-Scafati</surname><given-names>Orazio</given-names></name><xref ref-type="aff" rid="af3-marinedrugs-18-00005">3</xref></contrib><contrib contrib-type="author"><name><surname>Nakamura</surname><given-names>Fumiaki</given-names></name><xref ref-type="aff" rid="af4-marinedrugs-18-00005">4</xref></contrib><contrib contrib-type="author"><name><surname>Fusetani</surname><given-names>Nobuhiro</given-names></name><xref ref-type="aff" rid="af5-marinedrugs-18-00005">5</xref></contrib></contrib-group><aff id="af1-marinedrugs-18-00005"><label>1</label>Department of Pharmacology, College of Graduate Studies, Midwestern University, 555 31st Street, Downers Grove, IL 60515, USA;<email>aguerrero89@midwestern.edu</email></aff><aff id="af2-marinedrugs-18-00005"><label>2</label>Molecular Sciences Research Center, University of Puerto Rico, 1390 Ponce de León Avenue, San Juan, PR 00926, USA;<email>abimael.rodriguez1@upr.edu</email></aff><aff id="af3-marinedrugs-18-00005"><label>3</label>Department of Pharmacy, University of Naples “Federico II”, Via D. Montesano 49, I-80131 Napoli, Italy;<email>scatagli@unina.it</email></aff><aff id="af4-marinedrugs-18-00005"><label>4</label>Department of Chemistry and Biochemistry, Graduate School of Advanced Science and Engineering, Waseda University, 3-4-1 Okubo, Shinjuku-ku, Tokyo 169-8555, Japan;<email>what-will_be.x2@akane.waseda.jp</email></aff><aff id="af5-marinedrugs-18-00005"><label>5</label>Fisheries and Oceans Hakodate, Hakodate 041-8611, Japan;<email>anobu@fish.hokudai.ac.jp</email></aff><author-notes><corresp id="c1-marinedrugs-18-00005"><label>*</label>Correspondence: <email>amayer@midwestern.edu</email>; Tel.: +1-630-515-6951; Fax: +1-630-515-6295</corresp></author-notes><pub-date pub-type="epub"><day>19</day><month>12</month><year>2019</year></pub-date><pub-date pub-type="collection"><month>1</month><year>2020</year></pub-date><volume>18</volume><issue>1</issue><elocation-id>5</elocation-id><history><date date-type="received"><day>27</day><month>11</month><year>2019</year></date><date date-type="accepted"><day>14</day><month>12</month><year>2019</year></date></history><permissions><copyright-statement>© 2019 by the authors.</copyright-statement><copyright-year>2019</copyright-year><license license-type="open-access"><license-p>Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (<ext-link ext-link-type="uri" xlink:href="http://creativecommons.org/licenses/by/4.0/">http://creativecommons.org/licenses/by/4.0/</ext-link>).</license-p></license></permissions><abstract><p>The systematic review of the marine pharmacology literature from 2014 to 2015 was completed in a manner consistent with the 1998–2013 reviews of this series. Research in marine pharmacology during 2014–2015, which was reported by investigators in 43 countries, described novel findings on the preclinical pharmacology of 301 marine compounds. These observations included antibacterial, antifungal, antiprotozoal, antituberculosis, antiviral, and anthelmintic pharmacological activities for 133 marine natural products, 85 marine compounds with antidiabetic, and anti-inflammatory activities, as well as those that affected the immune and nervous system, and 83 marine compounds that displayed miscellaneous mechanisms of action, and may probably contribute to novel pharmacological classes upon further research. Thus, in 2014–2015, the <italic>preclinical</italic> marine natural product pharmacology pipeline provided novel pharmacology as well as new lead compounds for the <italic>clinical</italic> marine pharmaceutical pipeline, and thus continued to contribute to ongoing global research for alternative therapeutic approaches to many disease categories.</p></abstract><kwd-group><kwd>drug</kwd><kwd>marine</kwd><kwd>chemical</kwd><kwd>metabolite</kwd><kwd>natural product</kwd><kwd>pharmacology</kwd><kwd>pharmaceutical</kwd><kwd>review</kwd><kwd>toxicology</kwd><kwd>pipeline</kwd></kwd-group></article-meta></front><body><sec sec-type="intro" id="sec1-marinedrugs-18-00005"><title>1. Introduction</title><p>The aim of the present review is to consolidate 2014–2015 <italic>preclinical</italic> marine pharmacology, with a format similar to the previous nine reviews of this series, which cover the period 1998–2013 [<xref rid="B1-marinedrugs-18-00005" ref-type="bibr">1</xref>,<xref rid="B2-marinedrugs-18-00005" ref-type="bibr">2</xref>,<xref rid="B3-marinedrugs-18-00005" ref-type="bibr">3</xref>,<xref rid="B4-marinedrugs-18-00005" ref-type="bibr">4</xref>,<xref rid="B5-marinedrugs-18-00005" ref-type="bibr">5</xref>,<xref rid="B6-marinedrugs-18-00005" ref-type="bibr">6</xref>,<xref rid="B7-marinedrugs-18-00005" ref-type="bibr">7</xref>,<xref rid="B8-marinedrugs-18-00005" ref-type="bibr">8</xref>,<xref rid="B9-marinedrugs-18-00005" ref-type="bibr">9</xref>]. The peer-reviewed articles were retrieved from searches in the following databases: MarinLit, PubMed, Chemical Abstracts<sup>®</sup>, ISI Web of Knowledge, and Google Scholar. As in our previous work, we have limited our review to include bioactivity and/or pharmacology of structurally characterized marine chemicals, which we have classified using a modification of Schmitz’s chemical classification [<xref rid="B10-marinedrugs-18-00005" ref-type="bibr">10</xref>] into six major chemical classes, namely, polyketides, terpenes, peptides, alkaloids, shikimates, and sugars. The preclinical antibacterial, antifungal, antiprotozoal, antituberculosis, antiviral, and anthelmintic pharmacology of marine chemicals is reported in <xref rid="marinedrugs-18-00005-t001" ref-type="table">Table 1</xref>, with the structures shown in <xref ref-type="fig" rid="marinedrugs-18-00005-f001">Figure 1</xref>. Marine compounds that affected the immune and nervous systems, with antidiabetic and anti-inflammatory effects, are exhibited in <xref rid="marinedrugs-18-00005-t002" ref-type="table">Table 2</xref>, with their respective structures consolidated in <xref ref-type="fig" rid="marinedrugs-18-00005-f002">Figure 2</xref>. Finally, marine compounds affecting a variety of cellular and molecular targets are noted in <xref rid="marinedrugs-18-00005-t003" ref-type="table">Table 3</xref>, and their structures are shown in <xref ref-type="fig" rid="marinedrugs-18-00005-f003">Figure 3</xref>. </p><p>Several publications during 2014–2015 reported on several marine extracts or structurally uncharacterized compounds, with novel <italic>preclinical</italic> and/or <italic>clinical</italic> pharmacology: in vitro phenotype-guided the discovery of natural products using cytological profiling to predict modes of action of bioactive constituents in extracts [<xref rid="B11-marinedrugs-18-00005" ref-type="bibr">11</xref>]; Colombian and Brazilian marine organisms as source of <italic>antibacterial</italic> extracts with bacterial quorum sensing inhibitory activity [<xref rid="B12-marinedrugs-18-00005" ref-type="bibr">12</xref>]; a first report describing antimicrobial activity in extracts from cultivable fungi associated with Antarctic marine sponges [<xref rid="B13-marinedrugs-18-00005" ref-type="bibr">13</xref>]; an extensive study on the antimicrobial activity of crude extracts from several species of red algae from Madagascar [<xref rid="B14-marinedrugs-18-00005" ref-type="bibr">14</xref>]; bioactive compounds along with a purified macrolactin with broad spectrum antibacterial activity in crude extracts from <italic>B. subtilis</italic> MTCC10403 associated with the Indian brown seaweed <italic>A. longifolius</italic> [<xref rid="B15-marinedrugs-18-00005" ref-type="bibr">15</xref>]; potential β-lactamase inhibitory activity in a Bay of Bengal marine <italic>Streptomyces</italic> sp. PM49 with antibacterial properties on multidrug-resistant pathogens [<xref rid="B16-marinedrugs-18-00005" ref-type="bibr">16</xref>]; in vitro <italic>anti-inflammatory</italic> activity of an extract and individual components in the spiny seastar <italic>M. glacialis</italic> that inhibited “different levels of the inflammation pathway” [<xref rid="B17-marinedrugs-18-00005" ref-type="bibr">17</xref>]; in vitro anti-inflammatory activity of several galactolipids isolated from methanol extracts of cultivated red alga <italic>Chondrus crispus</italic> that were proposed “to counter inflammation associated with NO-mediated disorders” [<xref rid="B18-marinedrugs-18-00005" ref-type="bibr">18</xref>]; in vitro immunomodulatory activity of an extract of the Bohai sea ascidian <italic>Styela clava</italic> that exhibited proliferative activity and promoted nitric oxide (NO) release from mouse lymphocytes and macrophages [<xref rid="B19-marinedrugs-18-00005" ref-type="bibr">19</xref>]; in vivo anti-inflammatory activity of a new nucleoside, dragmacidoside isolated from an extract of a marine Red sea sponge <italic>Dragmacidon coccinea</italic> [<xref rid="B20-marinedrugs-18-00005" ref-type="bibr">20</xref>]; in vivo anti-inflammatory and analgesic activities of an organic extract and its semipurified fractions from the Tunisian gorgonian <italic>Eunicella singularis</italic>, which suggested that “components of the active fraction can be used to treat various anti-inflammatory diseases” [<xref rid="B21-marinedrugs-18-00005" ref-type="bibr">21</xref>]; in vitro anti-inflammatory activity of 30 compounds in a methanol extract of the digestive gland of the Mediterranean sea hare <italic>Aplysia depilans,</italic> which could provide “beneficial anti-inflammatory effects” [<xref rid="B22-marinedrugs-18-00005" ref-type="bibr">22</xref>]; and, as part of anti-obesity nutraceuticals research, the anti-adipogenic activity of phlorotannins isolated from the edible brown alga <italic>Ecklonia cava</italic> were reported to be a “promising source for utilization against obesity and related complications” [<xref rid="B23-marinedrugs-18-00005" ref-type="bibr">23</xref>].</p></sec><sec id="sec2-marinedrugs-18-00005"><title>2. Marine Compounds with Antibacterial, Antifungal, Antiprotozoal, Antituberculosis, Antiviral, and Anthelmintic Activities</title><p><xref rid="marinedrugs-18-00005-t001" ref-type="table">Table 1</xref> presents 2014–2015 preclinical pharmacological research on the antibacterial, antifungal, antiprotozoal, antituberculosis, antiviral, and anthelmintic activities of marine natural products (<bold>1</bold>–<bold>133</bold>) shown in <xref ref-type="fig" rid="marinedrugs-18-00005-f001">Figure 1</xref>.</p><sec id="sec2dot1-marinedrugs-18-00005"><title>2.1. Antibacterial Activity</title><p>During 2014–2015, 48 studies reported <italic>antibacterial</italic> marine natural products (<bold>1</bold>–<bold>64</bold>) isolated from bacteria, fungi, tunicates, sponges, soft corals, sea snakes, fish, and algae; a research enterprise focused on the discovery of novel chemical leads to treat emerging drug-resistant bacterial infections.</p><p>As shown in <xref rid="marinedrugs-18-00005-t001" ref-type="table">Table 1</xref> and <xref ref-type="fig" rid="marinedrugs-18-00005-f001">Figure 1</xref>, nine publications reported on the mode of action of marine-derived antibacterial compounds. Rodríguez and colleagues reported on “a practical synthesis of the axinellamines” (<bold>1</bold>, <bold>2</bold>), as well as their broad spectrum Gram-positive and Gram-negative antibacterial activity, probably resulting from “secondary membrane destabilization…consistent with the inhibition of normal septum formation” [<xref rid="B24-marinedrugs-18-00005" ref-type="bibr">24</xref>]. Moon and colleagues characterized a new pentacyclic antibiotic, buanmycin (<bold>3</bold>), isolated from a Korean marine <italic>Streptomyces</italic> strain, which was active towards Gram-native <italic>Salmonella enterica</italic> that causes salmonellosis, by inhibiting sortase A, an enzyme involved in bacterial adhesion and proposed as a “promising target for antibiotic discovery” [<xref rid="B25-marinedrugs-18-00005" ref-type="bibr">25</xref>]. Wei and colleagues discovered a novel peptide cathelicidin (<bold>4</bold>) from the Chinese sea snake <italic>Hydrophis cyanocinctus</italic> with potent antimicrobial activity against 35 strains of 48 human pathogenic bacteria, probably by a mechanism that involved “disruption of cell membrane and lysis of bacterial cells…resulting in cellular disruption of both Gram-positive and Gram-negative bacteria” [<xref rid="B26-marinedrugs-18-00005" ref-type="bibr">26</xref>]. Silva and colleagues demonstrated that the antimicrobial peptide clavanin A (<bold>5</bold>) significantly reduced <italic>E. coli</italic> and <italic>S. aureus</italic>-infected mice mortality with concomitant reduction of proinflammatory cytokines, thus proposing that clavalin A “… will facilitate studies on the development of novel peptide-based strategies for the treatment of infected wounds and sepsis” [<xref rid="B27-marinedrugs-18-00005" ref-type="bibr">27</xref>]. Abdelmohsen and colleagues investigated the new sterol gelliusterol E (<bold>6</bold>) from the Red sea sponge <italic>Callyspongia</italic> aff. <italic>implexa</italic> and showed that it inhibited both the primary infection by <italic>Chlamydia trachomatis</italic>, an obligate intracellular Gram-negative bacterium, as well as the production of viable progeny, and thus the developmental cycle of this bacterium [<xref rid="B28-marinedrugs-18-00005" ref-type="bibr">28</xref>]. Pieri and colleagues described new ianthelliformisamine B and C (<bold>7, 8</bold>) from the marine sponge <italic>Suberea ianthelliformis</italic> as antibiotic enhancers against resistant Gram-negative bacteria by a mechanism described as “altered proton homeostasis”, and thus probably affecting drug transport [<xref rid="B29-marinedrugs-18-00005" ref-type="bibr">29</xref>]. Huang and colleagues showed that the antimicrobial peptide pardaxin (<bold>9</bold>) isolated from the Red sea flatfish <italic>Pardachirus marmoratus</italic> protected mice from a lethal dose of methicillin-resistant <italic>Staphylococcus aureus</italic>, while also accelerating wound healing, increasing monocytes’ and macrophages’ recruitment, as well as expression of vascular endothelial growth factor [<xref rid="B30-marinedrugs-18-00005" ref-type="bibr">30</xref>]. Eom and colleagues described the mechanism of antibacterial activity of the phlorotannin phlorofucofuroeckol-A (<bold>10</bold>) isolated from the edible brown alga <italic>Eisenia bicyclis</italic>, which was shown to involve suppression of several <italic>mec</italic> operon genes in methicillin-resistant <italic>Staphylococcus aureus</italic> as well as the production of penicillin-binding protein 2a, considered as the “primary cause of methicillin resistance” [<xref rid="B31-marinedrugs-18-00005" ref-type="bibr">31</xref>]. Hassan and colleagues reported a new depsipeptide salinamide F (<bold>11</bold>), isolated from a marine-derived <italic>Streptomyces</italic> sp. strain CNB-091 that was observed to significantly inhibit RNA polymerase (RNAP) from both Gram-positive and Gram-negative bacteria, but “does not interact with the rifampin binding site on RNAP” [<xref rid="B32-marinedrugs-18-00005" ref-type="bibr">32</xref>].</p><p>As shown in <xref rid="marinedrugs-18-00005-t001" ref-type="table">Table 1</xref> and <xref ref-type="fig" rid="marinedrugs-18-00005-f001">Figure 1</xref>, 53 marine natural products (<bold>12</bold>–<bold>64</bold>), some of them novel, were reported to exhibit antibacterial activity with MICs <10 μg/mL or 10 μM against several Gram-positive and Gram-negative bacterial strains, although the mechanism of action for these compounds remained undetermined: two antimicrobial peptides, piscidins 3 and 4 (<bold>12, 13</bold>) originally isolated from the fish tilapia <italic>Oreochromis niloticus</italic> [<xref rid="B33-marinedrugs-18-00005" ref-type="bibr">33</xref>]; a new bisthiodiketopiperazine adametizine A (<bold>14</bold>), isolated from a marine sponge-derived fungus <italic>Penicillium adametzioides</italic> AS-53 [<xref rid="B34-marinedrugs-18-00005" ref-type="bibr">34</xref>]; two dimeric bromopyrrole alkaloids agelamadins A and B (<bold>15, 16</bold>), isolated from the Okinawan marine sponge <italic>Agelas</italic> sp. [<xref rid="B35-marinedrugs-18-00005" ref-type="bibr">35</xref>]; a butyrolactone derivative (<bold>17</bold>), isolated from the fermentation broth of a South China sea gorgonian <italic>Muricella abnormalis</italic>-derived <italic>Aspergillus</italic> sp. XS-20090B15 fungus [<xref rid="B36-marinedrugs-18-00005" ref-type="bibr">36</xref>]; a meroditerpene aszonapyrone A (<bold>18</bold>), isolated from the Thai marine sponge <italic>Chondrilla asutraliensis</italic>-associated fungus <italic>Neosartorya paulistensis</italic> (KUFC 7897) [<xref rid="B37-marinedrugs-18-00005" ref-type="bibr">37</xref>]; a new meroterpenoid, austalide R (<bold>19</bold>), from a fungus <italic>Aspergillus</italic> sp. isolated from the Mediterranean sponge <italic>Tethya aurantium</italic> [<xref rid="B38-marinedrugs-18-00005" ref-type="bibr">38</xref>]; a novel citrifelin B (<bold>20</bold>) with a unique tetracyclic framework was characterized from a co-culture of marine-derived fungi <italic>Penicillium citrinum</italic> and <italic>Beauveria felina</italic> [<xref rid="B39-marinedrugs-18-00005" ref-type="bibr">39</xref>]; a novel cyclohexadepsipeptide desmethylisaridin C1 (<bold>21</bold>) identified from a marine bryozoan-derived fungus <italic>Beauveria felina</italic> EN-135 [<xref rid="B40-marinedrugs-18-00005" ref-type="bibr">40</xref>]; two novel polybrominated diphenyl ethers (<bold>22, 23</bold>), isolated from the cosmopolitan marine sponge <italic>Dysidea</italic> spp. [<xref rid="B41-marinedrugs-18-00005" ref-type="bibr">41</xref>]; a new pentacyclic cytochalasin diaporthalasin (<bold>24</bold>), isolated from the marine-derived fungus <italic>Diaporthaceae</italic> sp. PSU-SP2/4 [<xref rid="B42-marinedrugs-18-00005" ref-type="bibr">42</xref>]; natural brominated furanones (<bold>25, 26</bold>), isolated from the marine alga <italic>Delisea pulchra</italic> [<xref rid="B43-marinedrugs-18-00005" ref-type="bibr">43</xref>]; a novel meroterpenoid aureol B (<bold>27</bold>), isolated from the Micronesian <italic>Dysidea</italic> sp. sponge [<xref rid="B44-marinedrugs-18-00005" ref-type="bibr">44</xref>]; a novel meroterpenoid dysidinoid A (<bold>28</bold>), isolated from the South China sea sponge <italic>Dysidea</italic> sp. [<xref rid="B45-marinedrugs-18-00005" ref-type="bibr">45</xref>]; a terpenoid fuscoside E peracetate (<bold>29</bold>) and a lipid batyl alcohol (<bold>30</bold>), isolated from the Colombian soft coral <italic>Eunicea</italic> sp. [<xref rid="B46-marinedrugs-18-00005" ref-type="bibr">46</xref>]; a new aromatic butyrolactone flavipesin A (<bold>31</bold>), isolated from a marine-derived endophytic fungus <italic>Aspergillus flavipes</italic> [<xref rid="B47-marinedrugs-18-00005" ref-type="bibr">47</xref>]; new non-cytotoxic lipopeptides gageopeptides A–D (<bold>32, 33, 34, 35</bold>) [<xref rid="B48-marinedrugs-18-00005" ref-type="bibr">48</xref>] and gageotetrins A–C (<bold>36, 37, 38</bold>) [<xref rid="B49-marinedrugs-18-00005" ref-type="bibr">49</xref>], isolated from a Korean marine-derived <italic>Bacillus subtilis</italic> strain 109GGC020; a new cyclic depsipeptide hormaomycin B (<bold>39</bold>), isolated from a Korean marine mudflat-derived actinomycete <italic>Streptomyces</italic> sp. strain SNM55 [<xref rid="B50-marinedrugs-18-00005" ref-type="bibr">50</xref>]; a new glycolipid ieodoglucomide C (<bold>40</bold>) from the Korean marine-derived bacterium <italic>Bacillus licheniformis</italic> strain 09IDYM23 [<xref rid="B51-marinedrugs-18-00005" ref-type="bibr">51</xref>]; a new polycyclic tetramic acid macrolactam isoikarugamycin (<bold>41</bold>) from Equatorial Guinean <italic>Streptomyces zhaozhouensis</italic> strain CA-185989 [<xref rid="B52-marinedrugs-18-00005" ref-type="bibr">52</xref>]; a bromopyrrole alkaloid keramadine (<bold>42</bold>), isolated from the Okinawan marine sponge <italic>Agelas</italic> sp. [<xref rid="B53-marinedrugs-18-00005" ref-type="bibr">53</xref>]; “unprecedented” 9,11 secosterols with “the 2-ene-1,4-dione moiety” (<bold>43, 44</bold>) from the Korean marine sponge <italic>Ircinia</italic> sp. [<xref rid="B54-marinedrugs-18-00005" ref-type="bibr">54</xref>,<xref rid="B55-marinedrugs-18-00005" ref-type="bibr">55</xref>]; two polybrominated diphenyl ethers (<bold>45, 46</bold>) from the Papuan New Guinea marine sponge <italic>Lendenfeldia dendyi</italic> and the soft coral <italic>Sinularia dura</italic> [<xref rid="B56-marinedrugs-18-00005" ref-type="bibr">56</xref>]; a novel polyketide lindgomycin (<bold>47</bold>) from the Baltic sea and Arctic Lindgomycetaceae family marine fungal strains KF970 and LF327 [<xref rid="B57-marinedrugs-18-00005" ref-type="bibr">57</xref>]; a novel cycloheptadepsipeptide marfomycin D (<bold>48</bold>)<bold>,</bold> isolated from a South China marine <italic>Streptomyces drozdowiczii</italic> SCSIO 10141 [<xref rid="B58-marinedrugs-18-00005" ref-type="bibr">58</xref>]; an glycohexadepsipeptide-polyketide mollemycin A (<bold>49</bold>) from an Australian marine-derived <italic>Streptomyces</italic> sp. strain CMB-M0244 [<xref rid="B59-marinedrugs-18-00005" ref-type="bibr">59</xref>]; a novel laurene-type sesquiterpene neolaurene (<bold>50</bold>) from a Bornean marine alga <italic>Laurencia nangii</italic> [<xref rid="B60-marinedrugs-18-00005" ref-type="bibr">60</xref>]; a new polyketide and ambuic acid analogue penicyclone A (<bold>51</bold>), isolated form an extract from a deep-sea derived fungus <italic>Penicillium</italic> sp. F23-2 [<xref rid="B61-marinedrugs-18-00005" ref-type="bibr">61</xref>]; a new phenolic enamide (<bold>52</bold>), characterized from the Chinese marine alga <italic>Codium fragile</italic>-derived endophytic fungus <italic>Penicillium oxalicum</italic> strain EN-290 [<xref rid="B62-marinedrugs-18-00005" ref-type="bibr">62</xref>]; a novel meroterpenoid puupehenol (<bold>53</bold>), isolated from a Hawaiian sponge <italic>Dactylospongia</italic> sp. [<xref rid="B63-marinedrugs-18-00005" ref-type="bibr">63</xref>]; a new scalarane sesterpene phyllospongin E (<bold>54</bold>), isolated from the Egyptian Red sea sponge <italic>Phyllospongia lamellosa</italic> [<xref rid="B64-marinedrugs-18-00005" ref-type="bibr">64</xref>]; two new rare pyrane-based cembranoids sarcotrocheliol acetate (<bold>55</bold>) and sarcotrocheliol (<bold>56</bold>), isolated from the Red sea soft coral <italic>Sarcophyton trocheliophorum</italic> [<xref rid="B65-marinedrugs-18-00005" ref-type="bibr">65</xref>]; a novel depsidone-based analogue spiromastixone J (<bold>57</bold>), isolated from the fermentation broth of a deep-sea <italic>Spiromastix</italic> sp. fungus [<xref rid="B66-marinedrugs-18-00005" ref-type="bibr">66</xref>]; a new spirocyclic drimane stachyin B (<bold>58</bold>), identified in the mycelia and culture broth of a North sea <italic>Stachybotrys</italic> sp. fungus strain MF347 [<xref rid="B67-marinedrugs-18-00005" ref-type="bibr">67</xref>]; a naphthacene glycoside SF2446A2 (<bold>59</bold>), isolated from a culture of <italic>Streptomyces</italic> sp. strain RV15 derived from the Mediterranean sponge <italic>Dysidea tupha</italic> [<xref rid="B68-marinedrugs-18-00005" ref-type="bibr">68</xref>]; three new subergosterones A–C (<bold>60</bold>–<bold>62</bold>), obtained from the South China sea gorgonian coral <italic>Subergorgia rubra</italic> [<xref rid="B69-marinedrugs-18-00005" ref-type="bibr">69</xref>]; an amino-polyketide vitroprocine A (<bold>63</bold>), isolated from the marine bacterium <italic>Vibrio</italic> sp. strain QWI-06 [<xref rid="B70-marinedrugs-18-00005" ref-type="bibr">70</xref>]; and a new polyacetylene derivative xestospongiamide (<bold>64</bold>), isolated from the Red sea sponge <italic>Xestospongia</italic> sp. [<xref rid="B71-marinedrugs-18-00005" ref-type="bibr">71</xref>].</p><p>Furthermore, during 2014–2015, several other marine natural products, some of them novel, reported antimicrobial activity in MICs or IC<sub>50</sub>’s ranging from 10 to 50 μg/mL, or 10–50 μM, respectively, and thus, because of their lower antibacterial potency, were <italic>excluded</italic> from <xref rid="marinedrugs-18-00005-t001" ref-type="table">Table 1</xref> and <xref ref-type="fig" rid="marinedrugs-18-00005-f001">Figure 1</xref>: tetracyclic sesterterpenes from a Korean marine sponge <italic>Clathria gombawuiensis</italic> sp. (MIC = 6.25–25 μg/mL) [<xref rid="B129-marinedrugs-18-00005" ref-type="bibr">129</xref>]; the antimicrobial peptide isolated from the mucus of the hagfish <italic>Myxine glutinosa</italic> and several structural analogs (MICs = 1.2–50 µM) [<xref rid="B130-marinedrugs-18-00005" ref-type="bibr">130</xref>]; bromopyrrole alkaloids agelamadins C–E (IC<sub>50</sub> = 32 μg/mL) from the Okinawan marine sponge <italic>Agelas</italic> sp. [<xref rid="B131-marinedrugs-18-00005" ref-type="bibr">131</xref>]; a new indole diterpenoid from the fungus <italic>Aspergillus flavus</italic> (MIC = 20.5 µM), isolated from the Chinese prawn <italic>Penaeus vannamei</italic> [<xref rid="B132-marinedrugs-18-00005" ref-type="bibr">132</xref>]; two new bromopyrrole alkaloids isolated from the Okinawan sponge <italic>Agelas</italic> sp., namely 2-debromomonagelamide U and 2-debromomukanadin G (MIC=32 μg/mL) [<xref rid="B133-marinedrugs-18-00005" ref-type="bibr">133</xref>]; seven known and one new sesquiterpene named epoxysubergorgic acid isolated from the Chinese gorgonian coral <italic>S. suberosa</italic> (MIC>8 μg/mL) [<xref rid="B134-marinedrugs-18-00005" ref-type="bibr">134</xref>]; a new bromotyrosine alkaloid aplysamine 8 (MIC=31 μg/mL) from an Australian marine sponge <italic>Pseudoceratina purpurea</italic> [<xref rid="B135-marinedrugs-18-00005" ref-type="bibr">135</xref>], alternariol derivatives (MIC = 50 μg/disk) from the endophytic fungus <italic>Alternaria alternata</italic> isolated from the Red sea soft coral <italic>Litophyton arboretum</italic> [<xref rid="B136-marinedrugs-18-00005" ref-type="bibr">136</xref>]; new polyketides amphidins C–F (MIC = 16 and 32 μg/mL), isolated from the culture broth of dinoflagellate <italic>Amphidinium</italic> sp. [<xref rid="B137-marinedrugs-18-00005" ref-type="bibr">137</xref>]; a new 1-deoxysphingoid, 3-<italic>epi</italic>-xestoaminol C (MIC = 32.6 µM), isolated from the New Zealand brown alga <italic>Xiphophora chondrophylla</italic> [<xref rid="B138-marinedrugs-18-00005" ref-type="bibr">138</xref>]; a new cyclic pentapeptide, asperpeptide A (MIC = 12.5 µM), isolated from the gorgonian-derived fungus <italic>Aspergillus</italic> sp. [<xref rid="B139-marinedrugs-18-00005" ref-type="bibr">139</xref>]; a nucleoside derivative, kipukasin H (MIC = 12.5 µM), isolated from the fungus <italic>A. versicolor</italic> derived from the Xisha islands, South China sea gorgonian <italic>D. gemmacea</italic> [<xref rid="B140-marinedrugs-18-00005" ref-type="bibr">140</xref>]; a new <italic>O</italic>-containing heterocyclic compound named felinone B (MIC = 32 μg/mL) from an extract of <italic>B. feline</italic> EN-135, a fungus isolated from an unidentified marine bryozoan [<xref rid="B141-marinedrugs-18-00005" ref-type="bibr">141</xref>]; new xanthone microluside A (MIC = 10–13 µM) from a Red sea marine sponge <italic>S. vagabunda</italic>-derived <italic>Micrococcus</italic> sp. EG45 [<xref rid="B142-marinedrugs-18-00005" ref-type="bibr">142</xref>]; a new cyclohexapeptide desotamide B (MIC = 12–16 μg/mL) from a South China sea marine microbe <italic>S. scopuliridis</italic> SCSIO ZJ46 [<xref rid="B143-marinedrugs-18-00005" ref-type="bibr">143</xref>]; new linear lipopeptides (MIC = 16 and 32 μg/mL) from a Korean marine <italic>Bacillus subtillis</italic> [<xref rid="B144-marinedrugs-18-00005" ref-type="bibr">144</xref>]; a new streptophenazine K (MIC = 14.5–21.6 µM) from bacteria isolated from a Baltic sea sponge <italic>Halichondria panacea</italic> [<xref rid="B145-marinedrugs-18-00005" ref-type="bibr">145</xref>]; a novel polyketide amantelide A (MIC = 32 µM) from a Guamanian Oscillatoriales cyanobacterium [<xref rid="B146-marinedrugs-18-00005" ref-type="bibr">146</xref>]; a novel echinomycin analog, quinomycin G (MIC = 16–64 μg/mL), isolated from <italic>Streptomyces</italic> sp. LS298 from a Hainan marine sponge <italic>Gelliodes carnosa</italic> [<xref rid="B147-marinedrugs-18-00005" ref-type="bibr">147</xref>]; and new cyclic lipopeptides gageopeptins A and B (MIC = 6 and 32 μg/mL) from a marine-derived strain <italic>Bacillus</italic> sp. 109GGC020 [<xref rid="B144-marinedrugs-18-00005" ref-type="bibr">144</xref>].</p></sec><sec id="sec2dot2-marinedrugs-18-00005"><title>2.2. Antifungal Activity</title><p>Sixteen studies during 2014–2015 reported on the <italic>antifungal</italic> activity of several marine natural products (<bold>64</bold>–<bold>83</bold>) isolated from marine bacteria, dinoflagellates, sponges, sea cucumbers, and algae, a slight increase from our last review [<xref rid="B9-marinedrugs-18-00005" ref-type="bibr">9</xref>] and previous reviews of this marine pharmacology series.</p><p>As shown in <xref rid="marinedrugs-18-00005-t001" ref-type="table">Table 1</xref> and <xref ref-type="fig" rid="marinedrugs-18-00005-f001">Figure 1</xref>, three reports described antifungal marine chemicals with novel mechanisms of action. Lee and colleagues investigated the new macrocyclic lactone antifungal bahamaolide A (<bold>65</bold>) isolated from the culture of marine actinomycete <italic>Streptomyces</italic> sp. CNQ343 [<xref rid="B72-marinedrugs-18-00005" ref-type="bibr">72</xref>]. Detailed studies determined that the compound inhibited isocitrate lyase (ICL) mRNA expression, suggesting it might be used for treatment of “<italic>C. albicans</italic> infections via inhibition of ICL activity”. Sugiyama and colleagues characterized the biological activity of the polyene macrolactam heronamide C (<bold>66</bold>) isolated from a marine-derived <italic>Streptomyces</italic> sp. [<xref rid="B73-marinedrugs-18-00005" ref-type="bibr">73</xref>]. The heronamide C was shown to induce abnormal cell wall morphology by “perturbing membrane microdomains”. Wyche and colleagues reported a novel marine-derived polyketide forazoline A (<bold>67</bold>) isolated from an <italic>Actinomadura</italic> sp. strain WMMB-499 cultivated from the ascidian <italic>Ecteinascidia turbinata</italic> [<xref rid="B74-marinedrugs-18-00005" ref-type="bibr">74</xref>]. Using chemical genomics, the authors proposed forazoline A worked in vivo in mice against the fungus <italic>Candida albicans</italic> by affecting cell membrane integrity by a “novel mechanism of action from known antifungal agents”.</p><p>As shown in <xref rid="marinedrugs-18-00005-t001" ref-type="table">Table 1</xref> and <xref ref-type="fig" rid="marinedrugs-18-00005-f001">Figure 1</xref>, several marine natural products showed antifungal activity with MICs that were either less than 10 μg/mL, 10 μM, or 10 μg/disk, but no mechanism of action studies were reported in the papers: an alkaloid aaptamine derivative (<bold>68</bold>), isolated from the South China sea sponge <italic>Aaptos aaptos</italic> [<xref rid="B75-marinedrugs-18-00005" ref-type="bibr">75</xref>]; a new linear polyketide amphidinin G (<bold>69</bold>), isolated from a Japanese symbiotic marine dinoflagellate <italic>Amphidinium</italic> sp. discovered in a marine flatworm <italic>Amphiscolops</italic> sp. [<xref rid="B76-marinedrugs-18-00005" ref-type="bibr">76</xref>]; a new polyketide amphidinol 18 (<bold>70</bold>), isolated from the dinoflagellate <italic>Amphidinium carterae</italic> strain CCMP121 [<xref rid="B77-marinedrugs-18-00005" ref-type="bibr">77</xref>]; new crambescin A2 (<bold>71</bold>–<bold>73</bold>), alkaloid homologues from the Bahamian marine sponge <italic>Pseudaxinella reticulata</italic> [<xref rid="B78-marinedrugs-18-00005" ref-type="bibr">78</xref>]; two new saponins cousteside C (<bold>74</bold>) and D (<bold>75</bold>), reported from the Egyptian Red sea cucumber <italic>Bohadschia cousteaui</italic> [<xref rid="B79-marinedrugs-18-00005" ref-type="bibr">79</xref>]; two new laurane-type sesquiterpenes, laurepoxyene (<bold>76</bold>) and 3β-hydroxyperoxyaplysin (<bold>77</bold>), and a new polyunsaturated fatty acid ethyl ester (<bold>78</bold>), isolated from the Chinese red alga <italic>Laurencia okamurai</italic> [<xref rid="B80-marinedrugs-18-00005" ref-type="bibr">80</xref>,<xref rid="B81-marinedrugs-18-00005" ref-type="bibr">81</xref>]; a novel dilactone-tethered pseudo-dimeric peptide mohangamide A (<bold>79</bold>), isolated from a Korean marine <italic>Streptomyces</italic> sp. [<xref rid="B82-marinedrugs-18-00005" ref-type="bibr">82</xref>]; a novel pleosporallin E (<bold>80</bold>), isolated from a marine fungus <italic>Pleosporales</italic> sp., discovered on the South China sea alga <italic>Enteromorpha clathrata</italic> [<xref rid="B83-marinedrugs-18-00005" ref-type="bibr">83</xref>]; a lysophospholipid (<bold>81</bold>), isolated from the South China sea sponge <italic>Spirastrella purpurea</italic> [<xref rid="B84-marinedrugs-18-00005" ref-type="bibr">84</xref>]; an acetylenic fatty acid derivative taurospongin A (<bold>82</bold>) from an Okinawan marine sponge SS-1202, family Spongiidae [<xref rid="B85-marinedrugs-18-00005" ref-type="bibr">85</xref>], and a new non-sulphated triterpene glycoside variegatuside D (<bold>83</bold>) from the south China sea cucumber <italic>Stichopus variegates</italic> [<xref rid="B86-marinedrugs-18-00005" ref-type="bibr">86</xref>]. Mechanism of action studies will be required to characterize the antifungal pharmacology of these marine-derived natural compounds.</p><p>In addition, novel structurally-characterized marine molecules with antifungal MICs or IC<sub>50</sub>’s greater than 10 μg/mL, 10 μM, or 10 μg/disk, which have been <italic>excluded</italic> from <xref rid="marinedrugs-18-00005-t001" ref-type="table">Table 1</xref> and <xref ref-type="fig" rid="marinedrugs-18-00005-f001">Figure 1</xref> because of their weaker bioactivity: a new bromopyrrole alkaloid mukanadine G (IC<sub>50</sub> = 8–16 μg/mL) isolated from the Okinawan marine sponge <italic>Agelas</italic> sp. [<xref rid="B53-marinedrugs-18-00005" ref-type="bibr">53</xref>]; a new C24-acetylenic acid, biemnic acid (MIC = 100 μg/disk) isolated from the Red sea sponge <italic>Biemna ehrenbergi</italic> [<xref rid="B148-marinedrugs-18-00005" ref-type="bibr">148</xref>]; two sulfated steroid-aminoacid conjugates isolated from the Irish marine sponge <italic>Polymastia boletiformis</italic> (MIC = 100 μg/disk) against <italic>C. albicans</italic> [<xref rid="B149-marinedrugs-18-00005" ref-type="bibr">149</xref>]; two novel lysophospholids from the Guanxi sponge <italic>S. purpurea</italic> (IC<sub>50</sub> = 16 and 32 μg/mL) [<xref rid="B84-marinedrugs-18-00005" ref-type="bibr">84</xref>]; two new bromotyrosine alkaloids, tyrokeradine G and H, isolated from an Okinawan Verongid marine sponge (MIC = 16 and 32 μg/mL) [<xref rid="B150-marinedrugs-18-00005" ref-type="bibr">150</xref>]; two highly brominated polyphenols isolated from the Qingdao red alga <italic>S. latiuscula</italic> (MIC = 12.5, 25 μg/mL) [<xref rid="B151-marinedrugs-18-00005" ref-type="bibr">151</xref>]; one novel anhydride metabolite, tubingenoic anhydride A (MIC = 330 μM), from the Mediterranean fungus <italic>A. tubingensis</italic> (Strain OY907) [<xref rid="B152-marinedrugs-18-00005" ref-type="bibr">152</xref>]; and a novel compound terretrione D (MIC = 32 μg/mL) from a tunicate-derived fungus <italic>Penicillium</italic> sp. CYE-97 [<xref rid="B153-marinedrugs-18-00005" ref-type="bibr">153</xref>]. These novel marine compounds may contribute to the antifungal preclinical and clinical pipeline upon further research. </p></sec><sec id="sec2dot3-marinedrugs-18-00005"><title>2.3. Antiprotozoal and Antituberculosis Activity</title><p>As shown in <xref rid="marinedrugs-18-00005-t001" ref-type="table">Table 1</xref>, during 2014–2015, twenty-four studies contributed to novel findings on <italic>antiprotozoal (antimalarial, antileishmanial, and antitrypanosomal)</italic> and <italic>antituberculosis</italic> pharmacology of structurally characterized marine natural products (<bold>84</bold>–<bold>112</bold>), very similar to our previous 1998–2013 marine pharmacology reviews [<xref rid="B1-marinedrugs-18-00005" ref-type="bibr">1</xref>,<xref rid="B2-marinedrugs-18-00005" ref-type="bibr">2</xref>,<xref rid="B3-marinedrugs-18-00005" ref-type="bibr">3</xref>,<xref rid="B4-marinedrugs-18-00005" ref-type="bibr">4</xref>,<xref rid="B5-marinedrugs-18-00005" ref-type="bibr">5</xref>,<xref rid="B6-marinedrugs-18-00005" ref-type="bibr">6</xref>,<xref rid="B7-marinedrugs-18-00005" ref-type="bibr">7</xref>,<xref rid="B8-marinedrugs-18-00005" ref-type="bibr">8</xref>,<xref rid="B9-marinedrugs-18-00005" ref-type="bibr">9</xref>].</p><p>Malaria, a global disease caused by protozoan genus <italic>Plasmodium</italic> (<italic>P. falciparum</italic>, <italic>P. ovale</italic>, <italic>P. vivax</italic> and <italic>P. malariae</italic>), currently affects over 2 billion people worldwide. Contributing to the global search for novel antimalarial drugs, and as presented in <xref rid="marinedrugs-18-00005-t001" ref-type="table">Table 1</xref>, 11 marine molecules (<bold>84</bold>–<bold>94</bold>) isolated from bacteria, molluscs, sponges, and soft corals were shown during 2014–2015 to possess <italic>antimalarial activity</italic>. Young and colleagues reported a detailed mechanistic study with the marine sesquiterpene isonitrile 7,20-diisocyanoadociane (<bold>84</bold>) originally isolated from the marine sponge <italic>Cymbastela hooperi</italic> [<xref rid="B87-marinedrugs-18-00005" ref-type="bibr">87</xref>], demonstrating that it inhibited β-hematin (IC<sub>50</sub> = 13nM), and thus interfered with the parasite’s heme detoxification pathway. </p><p>As shown in <xref rid="marinedrugs-18-00005-t001" ref-type="table">Table 1</xref> and <xref ref-type="fig" rid="marinedrugs-18-00005-f001">Figure 1</xref>, potent (IC<sub>50</sub> < 2 µM) to moderate (IC<sub>50</sub> > 2–10 µM) <italic>antimalarial</italic> activity was reported for several marine natural products (<bold>85</bold>–<bold>94</bold>), although the mechanism of action for these compounds remained undertermined at the time of publication. Cheng and colleagues reported potent antiplasmodial activity in the peptide actinoramide A (<bold>85</bold>) isolated from <italic>Streptomyces</italic> species “in all five (<italic>P. falciparum</italic>) lines retested” [<xref rid="B88-marinedrugs-18-00005" ref-type="bibr">88</xref>]. Yang and colleagues discovered that a novel norditerpene diacarperoxide J (<bold>86</bold>) isolated from the South China Sea sponge <italic>Diacarnus megaspinorhabdosa</italic> was a moderate growth inhibitor of <italic>P. falciparum</italic> D6 clone, and observed that the peroxy functional group might be a “potential pharmacophore” [<xref rid="B89-marinedrugs-18-00005" ref-type="bibr">89</xref>]. Thao and colleagues characterized cembranoid diterpene laevigatol A (<bold>87</bold>) from several Vietnamese soft corals with potent antimalarial activity against drug sensitive <italic>P. falciparum</italic> strain NF54 [<xref rid="B90-marinedrugs-18-00005" ref-type="bibr">90</xref>]. Raju and colleagues showed that the glycohexadepsipeptide-polyketide mollemycin A (<bold>49</bold>) isolated from an Australian marine-derived <italic>Streptomyces</italic> sp. strain CMB-M0244 strongly inhibited drug sensitive <italic>P. falciparum</italic> strain 3D7 and multidrug resistant strain Dd2 [<xref rid="B59-marinedrugs-18-00005" ref-type="bibr">59</xref>]. Avilés and colleagues noted that isocyanide amphilectane-type diterpenes monamphilectines B and C (<bold>88, 89</bold>), isolated from the Caribbean sponge <italic>Svenzea flava</italic>, exhibited strong inhibitory activity against <italic>P. falciparum</italic> strain 3D7 [<xref rid="B91-marinedrugs-18-00005" ref-type="bibr">91</xref>]. Gros and colleagues observed that among the novel tricyclid alkaloids isolated from the Madagascar marine sponge <italic>Biemna laboutei</italic> netamine K (<bold>90</bold>) exhibited inhibitory activity against several <italic>P. falciparum</italic> strains [<xref rid="B92-marinedrugs-18-00005" ref-type="bibr">92</xref>]. White and colleagues reported several novel isocyano/isothiocyanate sesquiterpenes (<bold>91–93</bold>) isolated from the nudibranch <italic>Phyllidia ocellata</italic> that showed strong antiplasmodial activity against drug resistant <italic>P. falciparum</italic> Dd2 and 3D7 strains [<xref rid="B93-marinedrugs-18-00005" ref-type="bibr">93</xref>]. Chianese and colleagues assessed antimalarial activity of the novel endoperoxide polyketide (<bold>94</bold>) from the South China sea marine sponge <italic>Plakortis simplex</italic> against the <italic>P. falciparum</italic> chloroquine-sensitive D10 and chloroquine-resistant W2 strains [<xref rid="B94-marinedrugs-18-00005" ref-type="bibr">94</xref>]. </p><p>As shown in <xref rid="marinedrugs-18-00005-t001" ref-type="table">Table 1</xref> and <xref ref-type="fig" rid="marinedrugs-18-00005-f001">Figure 1</xref>, thirteen marine compounds (<bold>95</bold>–<bold>107</bold>) isolated from bacteria, fungi, sponges, and soft corals were reported to possess bioactivity towards the so-called neglected protozoal diseases: leishmaniasis, caused by the genus <italic>Leishmania (L.</italic>); amebiasis, trichomoniasis, as well as African sleeping sickness (caused by <italic>Trypanosoma (T.) brucei rhodesiense</italic> and <italic>T. brucei gambiense</italic>), and American sleeping sickness or Chagas disease (caused by <italic>T. cruzi</italic>). </p><p>As shown in <xref rid="marinedrugs-18-00005-t001" ref-type="table">Table 1</xref>, two reports described two <italic>antitrypanosomal</italic> marine chemicals (<bold>95</bold>, <bold>96</bold>) as well as their mechanisms of action. Oli and colleagues examined the mode of action of plakortide E (<bold>95</bold>), isolated from the sponge <italic>Plakortis halichondrioides</italic>, and demonstrated that it inhibited activity of <italic>T. brucei</italic> by a non-competitive, covalent or “mechanisms leading to slow-binding”, reversible inhibition of the parasite’s enzyme rhodesain [<xref rid="B95-marinedrugs-18-00005" ref-type="bibr">95</xref>]. Santos and colleagues extended the pharmacology of guanidine and pyrimidine alkaloids from the Brazilian marine sponge <italic>Monanchora arbuscula</italic>, and reported that batzelladine L (<bold>96</bold>) affected both trypomastigotes of <italic>T. cruzi</italic> and <italic>L. infantum</italic> promastigotes, demonstrating that several mechanisms including altered plasma membrane permeability, mitochondrial membrane depolarization, and increased reactive oxygen species, probably contributing to “parasite cell death” [<xref rid="B96-marinedrugs-18-00005" ref-type="bibr">96</xref>]. </p><p>As shown in <xref rid="marinedrugs-18-00005-t001" ref-type="table">Table 1</xref> and <xref ref-type="fig" rid="marinedrugs-18-00005-f001">Figure 1</xref>, eleven additional marine natural products (<bold>97</bold>–<bold>107</bold>) exhibited <italic>antileishmanial</italic> and <italic>antiprotozoal</italic> activity, although their mechanisms of action remained undetermined. Abdelmohsen and colleagues reported that a new <italic>O</italic>-glycosylated angucycline actinosporin A (<bold>97</bold>), isolated from a culture of <italic>Actinokineospora</italic> sp. strain EG49 cultivated from a Red sea sponge <italic>Spheciospongia vagabunda</italic>, moderately inhibited the growth of <italic>T. brucei brucei</italic> [<xref rid="B97-marinedrugs-18-00005" ref-type="bibr">97</xref>]. Thao and colleagues isolated the terpenoid astropectenol A (<bold>98</bold>) from a Vietnamese marine sea star <italic>Astropecten polyacanthus</italic>, and observed significant activity against <italic>T. cruzi</italic> and <italic>T. brucei brucei</italic> [<xref rid="B98-marinedrugs-18-00005" ref-type="bibr">98</xref>]. Viegelmann and colleagues identified a new saringosterol derivative (<bold>99</bold>) from the Irish marine sponge <italic>Haliclona simulans</italic>, which demonstrated antitrypanosomal activity against <italic>T. brucei brucei</italic> [<xref rid="B99-marinedrugs-18-00005" ref-type="bibr">99</xref>]. Using genome-directed lead discovery, Schulze and colleagues contributed a novel polyene macrolactam lobosamide A (<bold>100</bold>) from a marine actinobacterium <italic>Micronospora</italic> sp. that was highly active towards the parasite <italic>T. brucei brucei,</italic> “likely via a parasite-specific mechanism” that remained undetermined [<xref rid="B100-marinedrugs-18-00005" ref-type="bibr">100</xref>]. Thao and colleagues assessed the cembranoid diterpenes lobocrasols A and C (<bold>101, 102</bold>), and crassumols D and E (<bold>104, 105</bold>), isolated from several Vietnamese soft corals, and noted that they displayed potent activity against <italic>L. donovani</italic> amastigotes and <italic>T. brucei rhodesiense,</italic> respectively [<xref rid="B90-marinedrugs-18-00005" ref-type="bibr">90</xref>]. Nakashima and colleagues found a new cyclopentadecane antibiotic mangromicin A (<bold>103</bold>) separated from the culture broth of the fungus <italic>Lechevalieria aerocolonigenes</italic> K10-0216 isolated from a Japanese mangrove sediment with potent activity against <italic>T. brucei brucei</italic> strain GUTat 3.1 [<xref rid="B101-marinedrugs-18-00005" ref-type="bibr">101</xref>]. Yang and colleagues characterized a new scalarane sesterterpene sesterstamide (<bold>106</bold>) isolated from the Paracel islands marine sponge <italic>Hyrtios</italic> sp. that moderately inhibited <italic>L. donovani</italic> promastigotes [<xref rid="B102-marinedrugs-18-00005" ref-type="bibr">102</xref>]. Von Salm and colleagues contributed a novel tricyclic sesquiterpenoid shagene A (<bold>107</bold>) from an “undescribed” soft coral collected from the “Scotia Arc in the Southern Ocean” that was moderately active against <italic>L. donovani</italic> [<xref rid="B103-marinedrugs-18-00005" ref-type="bibr">103</xref>].</p><p>Drug-resistant strains of the intracellular pathogen <italic>Mycobacterium tuberculosis</italic> have stimulated a search for novel drug leads with novel mechanisms of action, and, as shown in <xref rid="marinedrugs-18-00005-t001" ref-type="table">Table 1</xref> and <xref ref-type="fig" rid="marinedrugs-18-00005-f001">Figure 1</xref>, five novel marine natural products (<bold>108</bold>–<bold>112</bold>) isolated from sponges and fungi evidenced promising activity, and thus contributed to the ongoing global search for novel <italic>antituberculosis</italic> agents during 2014–2015.</p><p>Arai and colleagues identified a novel aaptamine class alkaloid, 2-methoxy-3-oxoaaptamine (<bold>108</bold>), from a marine sponge <italic>Aaptos</italic> sp. that demonstrated strong inhibitory activity against <italic>M. smegmatis</italic> in “both active growing and dormancy-inducing hypoxic conditions” [<xref rid="B104-marinedrugs-18-00005" ref-type="bibr">104</xref>]. Daletos and colleagues isolated cyclic peptides callyaerins A and B (<bold>109, 110</bold>), from the Indonesian sponge <italic>Callyspongia aerizusa</italic>, that demonstrated potent antibacterial activity against <italic>M. tuberculosis</italic>, highlighting the “potential of these compounds as promising anti-TB agents” [<xref rid="B105-marinedrugs-18-00005" ref-type="bibr">105</xref>]. Kumar and colleagues established that a new diarylpyrrole alkaloid denigrin C (<bold>111</bold>) from an extract of the Indian marine sponge <italic>Dendrilla nigra</italic> exhibited strong <italic>M. tuberculosis</italic> H<sub>37</sub>Rv activity “with a probable novel mechanism needed for antitubercular drug design…” [<xref rid="B106-marinedrugs-18-00005" ref-type="bibr">106</xref>]. Lin and colleagues characterized a racemic, prenylated polyketide dimer, oxazinin A (<bold>112</bold>) from a filamentous fungus isolated from the Papua New Guinea ascidian <italic>Lissoclinum patella</italic>, which showed activity against <italic>M. tuberculosis</italic> with modest activity towards human transient receptor potential channels [<xref rid="B107-marinedrugs-18-00005" ref-type="bibr">107</xref>].</p></sec><sec id="sec2dot4-marinedrugs-18-00005"><title>2.4. Antiviral Activity</title><p>As shown in <xref rid="marinedrugs-18-00005-t001" ref-type="table">Table 1</xref> and <xref ref-type="fig" rid="marinedrugs-18-00005-f001">Figure 1</xref>, twenty-one reports were published during 2014–2015 on the <italic>antiviral</italic> pharmacology of marine natural products (<bold>113</bold>–<bold>132</bold>) against human enterovirus 71, human cytomegalovirus, human immunodeficiency virus type-1 (HIV-1), human herpes simplex virus (HSV), influenza virus, hepatitis B virus, murine norovirus, respiratory syncytial virus (RSV), and sindbis virus.</p><p>As shown in <xref rid="marinedrugs-18-00005-t001" ref-type="table">Table 1</xref>, five reports described antiviral marine chemicals and their mechanisms of action. González-Almela and colleagues extended the pharmacology of pateamine A (<bold>113</bold>), isolated from the marine sponge <italic>Mycale</italic> sp. by demonstrating that the compound affected the translation of genomic and subgenomic mRNAs from Sindbis virus, although “subgenomic mRNA translation (was) more resistant to pateamine A inhibition” [<xref rid="B108-marinedrugs-18-00005" ref-type="bibr">108</xref>]. León and colleagues identified abyssomicin 2 (<bold>114</bold>) from a marine-derived actinobacterium <italic>Streptomyces</italic> sp. that reactivated human immunodeficiency virus type-1 (HIV-1) by a protein kinase C and histone deacetylase-independent mechanism that “remains to be elucidated” [<xref rid="B109-marinedrugs-18-00005" ref-type="bibr">109</xref>]. Karadeniz and colleagues reported that the anti-HIV activity of the phlorotannin derivative 8,4”’-dieckol (<bold>115</bold>) from the Korean brown alga <italic>Ecklonia cava</italic> included the “ability to act against drug-resistant HIV-1 strains” by a mechanism that involved inhibition of cytopathic effects, as well as inhibition of HIV-1 reverse transcriptase enzyme [<xref rid="B110-marinedrugs-18-00005" ref-type="bibr">110</xref>]. Zhao and colleagues established that truncateol M (<bold>116</bold>) isolated from a culture of the sponge-associated fungus <italic>Truncatella angustata</italic> demonstrated potent activity against influenza A infections by a mechanism that targeted the virion assembly and release step, putatively becoming “a model structure of antiviral lead for further modification” [<xref rid="B111-marinedrugs-18-00005" ref-type="bibr">111</xref>]. Chen and colleagues determined that the alkaloid neoechinulin B (<bold>117</bold>) isolated from the marine-derived fungus <italic>Eurotium rubrum</italic> showed potent inhibition of H1N1 influenza A virus by binding to the influenza virion envelope hemagglutin, thus “disrupting its interaction with the sialic acid receptor” on host cells [<xref rid="B112-marinedrugs-18-00005" ref-type="bibr">112</xref>]. </p><p>An additional 15 marine natural products (<bold>118</bold>–<bold>132</bold>), listed in <xref rid="marinedrugs-18-00005-t001" ref-type="table">Table 1</xref> and shown in <xref ref-type="fig" rid="marinedrugs-18-00005-f001">Figure 1</xref>, demonstrated antiviral activity, but the mechanism of action of these compounds remained undetermined at the time of publication. Li and colleagues isolated a novel khayanolide, thaixylomolin I (<bold>118</bold>) from the seeds of the Trang (South Thailand) mangrove plant <italic>Xylocarpus moluccensis</italic>, which inhibited potent activity against influenza virus strain H1N1 [<xref rid="B113-marinedrugs-18-00005" ref-type="bibr">113</xref>]. Chen and colleagues contributed a new prenylated dihydroquinolone derivative 22-<italic>O</italic>-(N-Me-L-valyl)-21-epi-aflaquinolone B (<bold>119</bold>), produced by the mycelia of an <italic>Aspergillus</italic> sp. fungus derived from a South China Sea gorgonian <italic>Muricella abnormaliz,</italic> that inhibited respiratory syncytial virus influenza A virus H1N1 “with a high therapeutic ratio” [<xref rid="B114-marinedrugs-18-00005" ref-type="bibr">114</xref>]. Nong and colleagues found that two novel lactones territrem D and arisugacin A (<bold>120, 121</bold>) from a fungus <italic>Aspergillus terreus</italic> SCSGAF0162 derived from a South China sea gorgonian <italic>Echinogorgia aurantiaca</italic> exhibited HSV-1 activity “under non-cytotoxic concentrations” [<xref rid="B115-marinedrugs-18-00005" ref-type="bibr">115</xref>]. Li and colleagues isolated a novel isoindolinone-type alkaloid chartarutine B (<bold>122</bold>) from the marine sponge-associated fungus <italic>Stachybotrys chartarum</italic>, which displayed moderate inhibitory activity HIV-1, noting that “side chain variation directly affected the inhibitory effects” [<xref rid="B116-marinedrugs-18-00005" ref-type="bibr">116</xref>]. Gupta and colleagues purified debromoaplysiatoxin (<bold>123</bold>) from the marine Singaporan cyanobacterium <italic>Trichodesmium erythraeum</italic>, which inhibited Chikungunya virus with “minimal cytotoxicity”, and probably targeted the viral replication cycle after “viral entry” [<xref rid="B117-marinedrugs-18-00005" ref-type="bibr">117</xref>]. Pardo-Vargas and colleagues reported that the new diterpene dolabelladienol A (<bold>124</bold>) isolated from the Brazilian marine brown alga <italic>Dictyota pfaffii</italic> had potent activity against HIV-1 and, owing to “low cytotoxicity”, appeared to be a “promising anti-HIV-1 agent” [<xref rid="B118-marinedrugs-18-00005" ref-type="bibr">118</xref>]. Cheng and colleagues noted that one of the dolastane diterpenes isolated from the South China sea brown alga <italic>Dictyota plectens</italic>, namely 13-deacetoxyamijidictyol (<bold>125</bold>), showed inhibitory activity against wild-type HIV-1 replication, thus proposing that “<italic>Dictyota</italic> algae may be a potential source of antiviral lead compounds” [<xref rid="B119-marinedrugs-18-00005" ref-type="bibr">119</xref>]. Yamashita and colleagues investigated the effect of two polybrominated diphenyl ethers (<bold>22, 23</bold>) isolated from the Indonesian marine sponge <italic>Dysidea granulosa</italic> on the hepatitis B virus (HBV) core promoter activity, as well as the production of HBV DNA, suggesting that they may become “candidate lead compounds for the development of anti-HBV drugs” [<xref rid="B120-marinedrugs-18-00005" ref-type="bibr">120</xref>]. Cao and colleagues discovered that a new steroid echrebsteroid C (<bold>126</bold>) from the South China sea gorgonian <italic>Echinogorgia rebekka</italic> evidenced high activity against respiratory syncytial virus, a common cause of lower respiratory tract disease in infants and children, as well as a high therapeutic index, thus “suggesting it might be useful as a potential antiviral agent” [<xref rid="B121-marinedrugs-18-00005" ref-type="bibr">121</xref>]. Jia and colleagues showed that one of two enantiomeric dimers, namely (+)-pestaloxazine A (<bold>127</bold>), isolated from a <italic>Pestalotiopsis</italic> sp. fungus derived from a soft coral, showed potent antiviral activity towards enterovirus 71, a small, single-stranded RNA virus that may cause hand, foot, and mouth disease associated with neurological complications in children and infants [<xref rid="B122-marinedrugs-18-00005" ref-type="bibr">122</xref>]. Eom and colleagues evaluated phlorofucofuroeckol-A (<bold>10</bold>), isolated from the edible brown alga <italic>Eisenia bicyclis</italic> against murine norovirus, a leading cause of gastroenteritis, noting that, because of its strong anti-norovirus activity and high therapeutic index, it appeared “phlorotannins could be used as a potential source of natural antiviral agents” [<xref rid="B123-marinedrugs-18-00005" ref-type="bibr">123</xref>]. Cheng and colleagues discovered a new <italic>seco</italic>-cembranoid secocrassumol (<bold>128</bold>) from the marine soft coral <italic>Lobophytum crassum</italic>, which showed significant activity against human cytomegalovirus, a common herpesvirus infection in humans [<xref rid="B124-marinedrugs-18-00005" ref-type="bibr">124</xref>]. Using ligand-based pharmacophore mapping, Dineshkumar and colleagues demonstrated that the polycyclic macrolide sporolide B (<bold>129</bold>) isolated from the marine actinomycete <italic>Salinispora tropica</italic> showed significant inhibition of the HIV-1 reverse transcriptase, and thus “could be a possible drug candidate for HIV” [<xref rid="B125-marinedrugs-18-00005" ref-type="bibr">125</xref>]. Shin and colleagues isolated two new depsipeptides stellettapeptins A and B (<bold>130, 131</bold>) from an extract of the Australian marine sponge <italic>Stelletta</italic> sp. with significant HIV-inhibitory properties, suggesting that “this class of peptides may hold promise as anti-HIV agents” [<xref rid="B126-marinedrugs-18-00005" ref-type="bibr">126</xref>]. Sun and colleagues characterized a new tetramic acid derivative trichobotrysin A (<bold>132</bold>) isolated from the culture of South China sea <italic>Trichobotrys effuse</italic> DFFSCS021 that inhibited herpes simplex virus type-1, responsible for lifelong oral infections in humans [<xref rid="B127-marinedrugs-18-00005" ref-type="bibr">127</xref>].</p></sec><sec id="sec2dot5-marinedrugs-18-00005"><title>2.5. Anthelmintic Activity</title><p>As shown in <xref rid="marinedrugs-18-00005-t001" ref-type="table">Table 1</xref>, only one report was published during 2014–2015 on the anthelmintic pharmacology of marine natural products. Farrugia and colleagues isolated a 6-<italic>N</italic>-acyladenine alkaloid, phorioadenine A (<bold>133</bold>), from the southern Australian marine sponge <italic>Phoriospongia</italic> sp., which displayed “…nematocidal activity against <italic>H. contortus</italic>…slightly weaker than commercial anthelmintics levamisole and closantel”, perhaps suggesting that this compound may become a promising lead compound for the development of new anthelmintics [<xref rid="B128-marinedrugs-18-00005" ref-type="bibr">128</xref>].</p></sec></sec><sec id="sec3-marinedrugs-18-00005"><title>3. Marine Compounds with Antidiabetic and Anti-Inflammatory Activity, and Affecting the Immune and Nervous System</title><p><xref rid="marinedrugs-18-00005-t002" ref-type="table">Table 2</xref> presents the 2014–2015 preclinical pharmacology of marine chemicals (<bold>134</bold>–<bold>218</bold>), which demonstrated either antidiabetic or anti-inflammatory activity, as well as affected the immune or nervous system, and whose structures are depicted in <xref ref-type="fig" rid="marinedrugs-18-00005-f002">Figure 2</xref>.</p><sec id="sec3dot1-marinedrugs-18-00005"><title>3.1. Antidiabetic Activity</title><p>As shown in <xref rid="marinedrugs-18-00005-t002" ref-type="table">Table 2</xref> and <xref ref-type="fig" rid="marinedrugs-18-00005-f002">Figure 2</xref>, four publications reported on the mode of action of marine-derived antidiabetic compounds (<bold>10</bold>, <bold>134</bold>–<bold>136</bold>). Kang and colleagues contributed to the pharmacology of diabetes by noting that the marine carotenoid fucoxanthin (<bold>134</bold>), isolated from the marine brown alga <italic>Ishige okamurae</italic>, protected cells and organs from oxidative damage induced by high glucose both in vitro and in vivo, concluding that “fucoxanthin may prove to be an effective mediator to control oxidative stress in hyperglycemia” [<xref rid="B155-marinedrugs-18-00005" ref-type="bibr">155</xref>]. Maeda and colleagues observed that fucoxanthin and its metabolite, fucoxanthinol (<bold>135</bold>), improved obesity-induced inflammation in adipocyte cells with concomitant suppression of tumor necrosis factor-α and monocyte chemotactic protein-1 RNA expression, thus concluding that fucoxanthin “ameliorates glucose tolerance in the diabetic mice model” [<xref rid="B154-marinedrugs-18-00005" ref-type="bibr">154</xref>]. Lee and colleagues reported that octaphlorethol A (<bold>136</bold>) isolated from the marine brown alga <italic>Ishige foliacea</italic> showed a potent anti-hyperglycemic effect in mice by potently binding to α-glucosidase, an enzyme that plays a role in blood glucose control, thus demonstrating its potential use “for treatment of type 2 diabetes mellitus” [<xref rid="B156-marinedrugs-18-00005" ref-type="bibr">156</xref>]. You and colleagues showed that the phlorotannin phlorofucofuroeckol-A (<bold>10</bold>) isolated from the brown alga <italic>Ecklonia cava</italic> alleviated postprandial hyperglycemia in diabetic mice by a mechanism that involved significant inhibition of α-glucosidase and α-amylase, thus proposing this natural product “as a nutraceutical for diabetic individuals” [<xref rid="B157-marinedrugs-18-00005" ref-type="bibr">157</xref>].</p><p>An additional six marine natural products (<bold>137</bold>–<bold>142</bold>), listed in <xref rid="marinedrugs-18-00005-t002" ref-type="table">Table 2</xref> and shown <xref ref-type="fig" rid="marinedrugs-18-00005-f002">Figure 2</xref>, demonstrated antidiabetic activity, but the mechanism of action of these compounds remained undetermined at the time of publication. Safavi-Hemami and colleagues described a specialized insulin Con-Ins G1 (<bold>137</bold>) used for chemical warfare by the fish-hunting cone snail <italic>Conus geographus</italic>, which appear to have “evolved to act rapidly and potently to cause severe hypoglycemia” [<xref rid="B158-marinedrugs-18-00005" ref-type="bibr">158</xref>]. Yamazaki and colleagues found that the sesquiterpene dehydroeuryspongin A (<bold>138</bold>) isolated from the Japanese marine sponge <italic>Euryspongia</italic> sp. inhibited the protein tyrosine phosphatase 1B, considered a key enzyme involved in type II diabetes and obesity because it plays a role in the dephosphorylation of insulin and leptin receptors [<xref rid="B159-marinedrugs-18-00005" ref-type="bibr">159</xref>]. Xia and colleagues contributed a new isopimarane diterpene (<bold>139</bold>) isolated from the culture of the fungus <italic>Epicoccum</italic> sp. associated with the marine sea cucumber <italic>Apostichopus japonicus</italic> that potently inhibited α-glucosidase [<xref rid="B160-marinedrugs-18-00005" ref-type="bibr">160</xref>]. Shin and colleagues isolated a new benzothioate glycoside suncheonoside A (<bold>140</bold>) from a Korean marine-derived <italic>Streptomyces</italic> strain that promoted adiponectin production during adipogenesis in vitro, thus “suggesting antidiabetic potential” [<xref rid="B161-marinedrugs-18-00005" ref-type="bibr">161</xref>]. You and colleagues reported that the lumazine-containing peptide terrelumamide A (<bold>141</bold>), isolated from the culture broth of the Korean marine-derived fungus <italic>Aspergillus terreus</italic>, improved insulin sensitivity and adiponectin production in an in vitro human adipogenesis model [<xref rid="B162-marinedrugs-18-00005" ref-type="bibr">162</xref>]. He and colleagues characterized a polyunsaturated lipid (<bold>142</bold>) from the Chinese marine sponge <italic>Xestospongia testudinaria</italic>, which was shown to inhibit protein tyrosine phosphatase 1B, considered as a significant target for the “treatment of type II diabetes and obesity” [<xref rid="B163-marinedrugs-18-00005" ref-type="bibr">163</xref>].</p></sec><sec id="sec3dot2-marinedrugs-18-00005"><title>3.2. Anti-Inflammatory Activity</title><p>As shown in <xref rid="marinedrugs-18-00005-t002" ref-type="table">Table 2</xref> and <xref ref-type="fig" rid="marinedrugs-18-00005-f002">Figure 2</xref>, there was a remarkable increase in anti-inflammatory pharmacology of marine compounds (<bold>143</bold>–<bold>191</bold>) during 2014–2015. The molecular mechanism of action of marine natural products (<bold>143</bold>–<bold>163</bold>) was assessed in both in vitro and in vivo preclinical pharmacological studies in twenty-two papers that used several in vitro models: the murine RAW 264.7 macrophages, a human keratinocyte cell line, a human hepatocarcinoma HepG2 cell line, primary rat brain microglia, and a murine microglia BV-2 cell line. </p><p>Taira and colleagues evaluated the anti-inflammatory properties of alcyonolide and its congener (<bold>143, 144</bold>), isolated from the Okinawan soft coral <italic>Cespitularia</italic> sp. in lipopolysaccharide (LPS)-stimulated RAW264.7, observing inhibition of NO as well as gene expression of the proinflammatory genes inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX)-2 mRNA [<xref rid="B164-marinedrugs-18-00005" ref-type="bibr">164</xref>]. Guo and colleagues extended the pharmacology of the terpenoid astaxanthin (<bold>145</bold>) by reporting that a reduction of oxidative stress in an in vivo model of rat burn injury was concomitant with a decrease in the level of malondialdehyde, an indicator of lipid peroxidation, as well as an increase of antioxidant enzymes superoxide dismutase and catalase, a “protective effect” that held “potential as a new drug treatment of severely burned patients…” [<xref rid="B165-marinedrugs-18-00005" ref-type="bibr">165</xref>]. Yang and colleagues reported that the polyketide 8,8′-bieckol (<bold>146</bold>), isolated from the edible marine brown alga <italic>Ecklonia cava</italic>, significantly inhibited both pro-inflammatory NO, prostaglandin E<sub>2</sub> (PGE<sub>2</sub>), and interleukin 6 (IL-6) production, as well as gene expression by downregulating NF-κB signaling pathway and ROS accumulation in both LPS-stimulated primary macrophages and RAW 264.7 macrophages, thus demonstrating the compound’s “anti-inflammatory potential…in systemic inflammatory conditions such as sepsis” [<xref rid="B166-marinedrugs-18-00005" ref-type="bibr">166</xref>]. Fernandes and colleagues studied convolutamydine A (<bold>147</bold>), isolated from marine bryozoan <italic>Amathia convoluta</italic>, and two synthesized analogs, and determined that they exhibited significant in vivo and in vitro anti-inflammatory activity by a mechanism that involved reduced leukocyte migration as well as inhibition of the production of the cytokine IL-6, PGE<sub>2</sub>, and NO [<xref rid="B167-marinedrugs-18-00005" ref-type="bibr">167</xref>]. Phan and colleagues isolated a new bicyclogermacrene capgermacrene A (<bold>148</bold>) from the Bornean soft coral <italic>Capnella</italic> sp. and observed significant in vitro inhibition of NO production by RAW 264.7 macrophages by inhibition of iNOS expression, proposing this compound as a “promising iNOS inhibiting agent” [<xref rid="B168-marinedrugs-18-00005" ref-type="bibr">168</xref>]. Jiménez-Romero and colleagues investigated the effect of the diterpene dactyloditerpenol acetate (<bold>149</bold>) extracted from the Puerto Rican tropical sea hare <italic>Aplysia dactylomela</italic> on <italic>E. coli</italic> LPS-activated rat neonatal microglia in vitro, observing the potent inhibition of both thromboxane B<sub>2</sub> and superoxide anion (O<sub>2</sub><sup>−</sup>) generation, proinflammatory mediators associated with neuroinflammation, concluding that the data “support further development” of this compound [<xref rid="B169-marinedrugs-18-00005" ref-type="bibr">169</xref>]. Two studies extended the anti-inflammatory pharmacology of dieckol (<bold>150</bold>) isolated from the brown alga <italic>Ecklonia cava</italic>: Choi and colleagues demonstrated the compound inhibited LPS-induced iNOS expression by affecting mitogen-activated protein kinases (MAPK), “significantly p38MAPK” in the mouse macrophage 264.7 cell line in vitro [<xref rid="B170-marinedrugs-18-00005" ref-type="bibr">170</xref>], while Kang and colleagues demonstrated that dieckol suppressed production of macrophage-derived chemokine, C–C motif chemokine 22, an inflammatory chemokine that controls leukocyte movements by down-regulating the activation of the signal transducer and activator of transcription (STAT)1 signaling pathway in human keratinocytes [<xref rid="B171-marinedrugs-18-00005" ref-type="bibr">171</xref>]. Lin and colleagues characterized the anti-inflammatory effects of the diterpene excavatolide B (<bold>151</bold>) isolated from the cultured Formosan marine gorgonian <italic>Briareum excavatum</italic> and observed that, in vitro, it inhibited iNOS and COX-2 mRNA expression in LPS-treated murine RAW 264.7 macrophages, while in vivo it attenuated carrageenan-induced rat paw inflammation and pain, thus concluding that “excavatolide B may serve as a useful therapeutic agent for the treatment of acute inflammation” [<xref rid="B172-marinedrugs-18-00005" ref-type="bibr">172</xref>]. Chen and colleagues investigated the antinociceptive properties of flexibilide (<bold>152</bold>), isolated from the Australian soft coral <italic>Sinularia flexibilis</italic> in the rat chronic injury model of neuropathic pain, observing significant analgesic effects concomitant with suppression of iNOS expression in microglia and astrocytes in the spinal dorsal horn, accompanied with upregulation of transforming growth factor-β1 (TGF-β1), “suggesting involvement of TGF-β1 in the anti-neuroinflammatory and analgesic effects” [<xref rid="B173-marinedrugs-18-00005" ref-type="bibr">173</xref>]. Kim and colleagues reported that a polyhydroxyflavone (<bold>153</bold>) isolated from the marine alga <italic>Hizikia fusiforme</italic> suppressed LPS-stimulated RAW 264.7 cells’ release of pro-inflammatory cytokines, as well as both iNOS and COX-2 expression, by attenuating nuclear transcription factor-κB (NF-κB) translocation, and thus might become a “potential therapeutic agent for patients with, or at risk of, septic shock or other inflammatory diseases” [<xref rid="B174-marinedrugs-18-00005" ref-type="bibr">174</xref>]. Wijesinghe and colleagues evaluated 5β-hydroxypalisadin B (<bold>154</bold>), a brominated secondary metabolite isolated from the Malaysian marine red alga <italic>Laurencia snackeyi</italic>, on LPS-stimulated RAW 264.7 macrophages and observed significant reduction of several pro-inflammatory cytokines, NO, and PGE<sub>2</sub> generation, and thus concluded that the compound might help development of “an active ingredient in pharmaceutical, nutraceutical…” applications [<xref rid="B175-marinedrugs-18-00005" ref-type="bibr">175</xref>]. Huang and colleagues characterized two novel biscembranes glaucumolides A and B (<bold>155, 156</bold>) from the cultured soft coral <italic>Sarcophyton glaucum</italic> that significantly inhibited O<sub>2</sub><sup>-</sup> generation and elastase release in human neutrophils, while also reducing expression of iNOS and COX-2 in LPS-treated murine RAW 264.7 macrophages, concluding that these two compounds “might be useful for future biomedical applications” [<xref rid="B176-marinedrugs-18-00005" ref-type="bibr">176</xref>]. Yu and colleagues determined that the effects of phlorofucofuroeckol-B (<bold>157</bold>), isolated from the marine alga <italic>Ecklonia stolonifera</italic>, on the decreased production of pro-inflammatory mediators by LPS-stimulated BV-2 microglia cells, as well as reduced COX-2 and iNOS expression, resulted from inhibition of the iκB-α/NF-κB and Akt/ERK/JNK pathways, thus proposing that this compound might be “considered as a therapeutic agent against neuroinflammation” [<xref rid="B177-marinedrugs-18-00005" ref-type="bibr">177</xref>]. Babskota and colleagues isolated a new phosphatidylglycerol (<bold>158</bold>) from an extract of the marine red alga <italic>Palmaria palmata</italic>, also commonly known as dulse, which strongly inhibited NO release from LPS treated murine RAW 264.7 macrophages, probably by a mechanism that down-regulated iNOS, thus suggesting that “consumption of dulse as a functional food may help to reduce inflammation associated with various diseases“ [<xref rid="B178-marinedrugs-18-00005" ref-type="bibr">178</xref>]. Itoh and coleagues showed that reduced scytonemin (<bold>159</bold>) isolated from the cosmopolitan colonial cyanobacterium <italic>Nostoc commune</italic> strongly inhibited LPS and interferon-γ-induced NO production in murine macrophage RAW 264.7 macrophages, by generating reactive oxygen species by activation of the phosphatidylinositol-3-kinase/Akt and the p38 mitogen-activated protein kinase/nuclear factor erythroid 2-related factor 2 signaling pathways [<xref rid="B179-marinedrugs-18-00005" ref-type="bibr">179</xref>]. Lillsunde and colleagues reported that a norcembranoid sinuleptolide (<bold>160</bold>) isolated from the Indian soft coral <italic>Sinularia kavarattiensis</italic> potently modulated both morphology and release of pro-inflammatory and anti-inflammatory mediators by LPS-treated rat primary microglial cells in vitro, thus decreasing microglia activation, which has been hypothesized to be involved in the “progression of chronic neurodegenerative diseases.. and central nervous system (CNS) homeostasis” [<xref rid="B180-marinedrugs-18-00005" ref-type="bibr">180</xref>]. Thao and colleagues contributed a new polyhydroxylated steroid sarcopanol A (<bold>161</bold>) from the Vietnamese soft coral <italic>Sarcophyton pauciplicatum</italic> that inhibited tumor necrosis factor (TNF)-α and interferon (IFN)γ-induced expression of COX-2, iNOS, and intercellular adhesion molecule-1 (ICAM-1) in the spontaneously transformed immortal human keratinocyte cell line HaCaT via inhibition of NF-κB signaling pathway activation [<xref rid="B181-marinedrugs-18-00005" ref-type="bibr">181</xref>]. Thao and colleagues investigated the diterpenoid sinumaximol (<bold>162</bold>), isolated from the marine soft coral <italic>Sinularia maxima</italic>, and determined that it significantly inhibited TNF-α-induced NF-κB transcriptional activity in a human hepatocarcinoma HepG2 cell line, while concomitantly inhibiting the expression of pro-inflammatory iNOS and ICAM-1mRNA expression, thus supporting the “therapeutic potential as anti-inflammatory” of this compound [<xref rid="B182-marinedrugs-18-00005" ref-type="bibr">182</xref>]. Quang con colleagues determined that tanzawaic acid A (<bold>163</bold>), isolated from a marine fungus <italic>Penicillium</italic> sp. SF-6013 derived from the Pacific sea urchin <italic>Brisaster latifrons</italic>, inhibited both NO and PGE<sub>2</sub> production from LPS-activated murine BV-2 microglia cells and RAW 264.7 murine macrophages, while suppressing iNOS and COX-2 expression and inhibiting protein tyrosine phosphatase 1B [<xref rid="B183-marinedrugs-18-00005" ref-type="bibr">183</xref>]. </p><p>In contrast to the marine compounds (<bold>143</bold>–<bold>163</bold>) with described anti-inflammatory mechanisms of action described in the preceding paragraph, and as shown in <xref rid="marinedrugs-18-00005-t002" ref-type="table">Table 2</xref>, for marine compounds (<bold>164</bold>–<bold>191</bold>), only anti-inflammatory activity (IC<sub>50</sub>) was reported, but the molecular mechanism of action of these marine-derived compounds remained undetermined at the time of publication: a new highly oxygenated meroterpene aspertetranone D (<bold>164</bold>) isolated from the marine algal-associated fungus <italic>Aspergillus</italic> sp. ZL0-1b14 [<xref rid="B184-marinedrugs-18-00005" ref-type="bibr">184</xref>]; a novel 6,12-dichlorobriarene diterpenoid briarenolide J (<bold>165</bold>), two briarane diterpenoids briarenolides K and L (<bold>166, 167</bold>), and the briarenolides U–W (<bold>168</bold>–<bold>169</bold>), all compounds isolated from the Taiwanese octocoral <italic>Briareum</italic> sp. [<xref rid="B185-marinedrugs-18-00005" ref-type="bibr">185</xref>,<xref rid="B186-marinedrugs-18-00005" ref-type="bibr">186</xref>,<xref rid="B187-marinedrugs-18-00005" ref-type="bibr">187</xref>]; two new briarane diterpenoids briaviolides E and I (<bold>170, 171</bold>), isolated from the Taiwanese soft coral <italic>Briareum violacea</italic> [<xref rid="B188-marinedrugs-18-00005" ref-type="bibr">188</xref>]; a new pigmented phenazine compound dermacozine H (<bold>172</bold>), isolated from the actinomycete <italic>Dermacoccus abyssi</italic> sp. nov. strain MT1.1, isolated from a Mariana Trench sediment at a depth of 10,898 m [<xref rid="B189-marinedrugs-18-00005" ref-type="bibr">189</xref>]; a novel sesquiterpene dysifragilone A (<bold>173</bold>), isolated from the South China Sea sponge <italic>Dysidea fragilis</italic> [<xref rid="B190-marinedrugs-18-00005" ref-type="bibr">190</xref>]; a new xenicane 4α-hydroxypachylactone (<bold>174</bold>), isolated from a Chinese brown alga <italic>Dictyota plectens</italic> [<xref rid="B191-marinedrugs-18-00005" ref-type="bibr">191</xref>]; a polyketide comaparvin (<bold>175</bold>), isolated from the Taiwanese marine crinoid <italic>Comanthus bennetti</italic> [<xref rid="B192-marinedrugs-18-00005" ref-type="bibr">192</xref>]; two novel eunicellin-type diterpenoids hirsutalins N and S (<bold>176, 177</bold>) and a new tocopherol-derived metabolite hirsutocospiro A (<bold>178</bold>), isolated from the Taiwanese soft coral <italic>Cladiella hirsuta</italic> [<xref rid="B193-marinedrugs-18-00005" ref-type="bibr">193</xref>,<xref rid="B194-marinedrugs-18-00005" ref-type="bibr">194</xref>,<xref rid="B195-marinedrugs-18-00005" ref-type="bibr">195</xref>]; a new cembranoid isosinulaflexiolide K (<bold>179</bold>), isolated from cultured Taiwanese soft corals <italic>Sinularia sandensis</italic> and <italic>Sinularia flexibilis</italic> [<xref rid="B196-marinedrugs-18-00005" ref-type="bibr">196</xref>]; a novel 9,11-secogorgosteroid klyflaccisteroid F (<bold>180</bold>), isolated from the Taiwaneses soft coral <italic>Klyxum flaccidum</italic> [<xref rid="B197-marinedrugs-18-00005" ref-type="bibr">197</xref>]; new eunicellin-type diterpenoids krempfielins N (<bold>181</bold>), Q (<bold>182</bold>), and R (<bold>183</bold>), isolated from a Taiwanese soft coral <italic>Cladiella krempfi</italic> [<xref rid="B198-marinedrugs-18-00005" ref-type="bibr">198</xref>,<xref rid="B199-marinedrugs-18-00005" ref-type="bibr">199</xref>]; a methylfarnesylquinone (<bold>184</bold>), isolated from the Taiwanese marine brown alga <italic>Homeostrichus formosana</italic> [<xref rid="B200-marinedrugs-18-00005" ref-type="bibr">200</xref>]; a novel steroid monanchosterol B (<bold>185</bold>), isolated from the Korean sponge <italic>Monanchora</italic> sp. [<xref rid="B201-marinedrugs-18-00005" ref-type="bibr">201</xref>]; a oxygenated steroid derivative (<bold>186</bold>), isolated from the Vietnamese starfish <italic>Protoreaster nodosus</italic> [<xref rid="B202-marinedrugs-18-00005" ref-type="bibr">202</xref>]; a new spirobisnaphthalene rhytidenone C (<bold>187</bold>), isolated from an extract of a cultured fungal endophyte <italic>Rhytidhysteron</italic> sp. AS21B isolated from a Thailandese mangrove area [<xref rid="B203-marinedrugs-18-00005" ref-type="bibr">203</xref>]; a known terpenoid sarcocrassocolide E (<bold>188</bold>), isolated from a Taiwanese soft coral <italic>Sarcophyton crassocaule</italic> [<xref rid="B204-marinedrugs-18-00005" ref-type="bibr">204</xref>]; a new cembrane diterpenoid sinulacembranolide A (<bold>189</bold>), isolated from the Taiwanese soft coral <italic>Sinularia gaweli</italic> [<xref rid="B205-marinedrugs-18-00005" ref-type="bibr">205</xref>]; a new eudesmane-type sesquiterpene thomimarine B (<bold>190</bold>), isolated from the fungus <italic>Penicillium thomii</italic> KMM 4667 isolated from the Japanese sea grass <italic>Zostera marina</italic> [<xref rid="B206-marinedrugs-18-00005" ref-type="bibr">206</xref>]; and a novel diterpenoid tortuosene A (<bold>191</bold>), isolated from the Taiwanese soft coral <italic>Sarcophyton tortuosum</italic> [<xref rid="B207-marinedrugs-18-00005" ref-type="bibr">207</xref>].</p></sec><sec id="sec3dot3-marinedrugs-18-00005"><title>3.3. Marine Compounds with Activity on the Immune System</title><p>As shown in <xref rid="marinedrugs-18-00005-t002" ref-type="table">Table 2</xref> and <xref ref-type="fig" rid="marinedrugs-18-00005-f002">Figure 2</xref>, the preclinical pharmacology of marine compounds that affected the <italic>immune</italic> system showed a decline, as previously reported in this series.</p><p>Kwan and colleagues reported that the peptide grassypeptolide A (<bold>192</bold>), isolated from the marine cyanobacterium <italic>Lyngbya confervoides,</italic> inhibited IL-2 production and proliferation of activated T cells by inhibiting the protease dipeptidyl peptidase 8, probably by binding at inner cavity of the enzyme at two distinct sites [<xref rid="B208-marinedrugs-18-00005" ref-type="bibr">208</xref>]. Wang and colleagues isolated a pair of novel bisheterocyclic quinolone-imidazole alkaloids (+)- and (<sup>_</sup>) spiroreticulatine (<bold>193</bold>) from the South China sea sponge <italic>Fascaplysinopsis reticulata</italic>, which showed inhibition of IL-2 production by Jurkat T cells [<xref rid="B209-marinedrugs-18-00005" ref-type="bibr">209</xref>]. Kicha and colleagues determined that the cyclic steroid glycoside luzonicoside A (<bold>194</bold>), isolated from the starfish <italic>Echinaster luzonicus</italic>, potently enhanced lysosomal activity, ROS level elevation, and NO synthesis in RAW 264.7 murine macrophages, thus seeming “promising for further investigation as a potent immunomodulatory agent” [<xref rid="B210-marinedrugs-18-00005" ref-type="bibr">210</xref>]. Pislyagin and colleagues investigated a triterpene glycoside typicoside C<sub>1</sub> (<bold>195</bold>), isolated from the sea cucumber <italic>Actinocucumis typica</italic>, and observed that it demonstrated strong immunostimulatory effect on ROS formation in mouse peritoneal macrophages in vitro, with concomitant low cytotoxicity [<xref rid="B211-marinedrugs-18-00005" ref-type="bibr">211</xref>]. </p></sec><sec id="sec3dot4-marinedrugs-18-00005"><title>3.4. Marine Compounds Affecting the Nervous System</title><p>As shown in <xref rid="marinedrugs-18-00005-t002" ref-type="table">Table 2</xref> and <xref ref-type="fig" rid="marinedrugs-18-00005-f002">Figure 2</xref>, in 2014–2015, the preclinical marine <italic>nervous</italic> system pharmacology of compounds (<bold>196</bold>–<bold>211</bold>) described several mechanism of action: at the nicotinic acetylcholine receptor and potassium channels, with conopeptides, and in models of antinociception and neuroprotection. </p><p>Four marine compounds were shown to bind nicotinic acetylcholine receptors (nACHR) (<bold>199</bold>, <bold>207</bold>, <bold>210</bold>) and potassium (K<sup>+</sup>) channels (<bold>208</bold>). Kasheverov and colleagues determined the effect of 6-bromohypaphorine (6-BHP) (<bold>199</bold>), isolated from the marine nudibranch mollusk <italic>Hermissenda crassicornis</italic>, on different nAChR, demonstrating that, because 6-BHP competed with α-bungarotoxin for binding to the human α7 nAChR, it was the “first low-molecular weight compound from (a) marine source which (was) an agonist of the nACHR subtype” [<xref rid="B215-marinedrugs-18-00005" ref-type="bibr">215</xref>]. Bourne and colleagues conducted detailed studies to determine the molecular pharmacology of the macrocylic imine phycotoxin pinnatoxin A (<bold>207</bold>), originally isolated from the digestive glands of the mollusk <italic>Pinna attenuata</italic>, towards neuronal α7nACHR, observing that the bicyclic EF-ketal ring was a novel binding determinant for mediating polar versus non-polar interactions, and thus is able to “confer nAChR subtype selectivity… (of) these prevalent marine biotoxins” [<xref rid="B223-marinedrugs-18-00005" ref-type="bibr">223</xref>]. Rodríguez and colleagues discovered a novel peptide PhcrTx1 (<bold>208</bold>) from the sea anemone <italic>Phymanthus crucifer</italic> that inhibited voltage-gated K<sup>+</sup> ion channels, including acid-sensing ion channel (ASIC) (IC<sub>50</sub> = 100 nM), and that would represent “the first member of a new structural group of sea anemone toxins acting on ASIC” [<xref rid="B224-marinedrugs-18-00005" ref-type="bibr">224</xref>]. Aráoz and colleagues extended the pharmacology of the “fast-acting” lipophilic marine toxin 13,19-desmethyl spirolide C (<bold>210</bold>), extracted from cultures of the dinoflagellate <italic>Alexandrium ostenfeldii</italic>, defining the mode of action and molecular targets using in vitro electrophysiological experiments, and thus showing that the toxin blocked human neuronal nACHR (IC<sub>50</sub> = 0.2 nM) with high affinity, observations supported by molecular docking experiments “highlighting the nicotinic basis of the neurotoxicity of (this toxin) to mammal(ian)….peripheral and central nervous system” [<xref rid="B227-marinedrugs-18-00005" ref-type="bibr">227</xref>].</p><p>Three studies extended the pharmacology of conopeptides (<bold>201</bold>–<bold>203</bold>). Wang and colleagues discovered a novel α-conotoxin Mr1.7 (<bold>201</bold>) in the venom of the marine snail <italic>Conus marmoreus</italic> that inhibited α3β2, α9α10, and α6/α3β2β3 nACHR subtypes (IC<sub>50</sub> = 53.1, 185.7, and 284.2 nM, respectively), noting that the PE residues at the N-terminal sequence of Mr1.7 were “important for modulating activity and selectivity” [<xref rid="B217-marinedrugs-18-00005" ref-type="bibr">217</xref>]. Zhou and colleagues reported the expression and sodium channel activity of peptide It16a (<bold>202</bold>), a novel framework XVI conotoxin from the M-superfamily isolated from the worm-hunting snail <italic>C. litteratus,</italic> and, using a variety of electrophysiological techniques, demonstrated that it preferentially inhibited voltage-gated Na<sup>+</sup> channels (apparent IC<sub>50</sub> = 1 µM) in mammalian sensory neurons, with the authors noting “It16a …has similar function as µ-conotoxins” [<xref rid="B218-marinedrugs-18-00005" ref-type="bibr">218</xref>]. Li and colleagues extended the pharmacology of Vt3.1 conotoxin (<bold>203</bold>), isolated from the venom of the marine cone snail <italic>C. vitulinus</italic>, and demonstrated that it preferentially inhibited large conductance, voltage, and Ca<sup>2+</sup> activated K<sup>+</sup> (BK) channels containing the <italic>β</italic>4 subunit (IC<sub>5</sub> = 8.5 µM), which appears to be present in brain and neuronal functions by a mechanism that required electrostatic interactions with the channel protein, making it an excellent tool “uniquely suited in neuroscience involving BK channels” [<xref rid="B219-marinedrugs-18-00005" ref-type="bibr">219</xref>]. </p><p>Two studies reported marine compounds (<bold>198</bold>, <bold>200</bold>) that contributed to nociceptive pharmacology. Cavalcante-Silva and colleagues assessed the mechanism involved in in vivo antinociception produced by the bisindole alkaloid caulerpine (<bold>198</bold>), isolated from the marine alga <italic>Caulerpa</italic>, demonstrating that, in the in vivo murine writhing test, the effect was likely mediated by “pathways involving α2-adrenoceptors and 5-HT3 receptors”, thus proposing cualerpine as a possible “dual-action analgesic drug(s)” [<xref rid="B214-marinedrugs-18-00005" ref-type="bibr">214</xref>]. Chen and colleagues investigated the anti-neuropathic properties of the antimicrobial peptide piscidin (<bold>200</bold>) and observed that the compound demonstrated in vivo anti-nociceptive effects in a rat model of neuropathy by a signaling mechanism that suppressed up-regulation of interleukin-1 in microglia and phosphorylated mammalian target of rapamycin in astrocytes, concluding it “may have potential for development as an alternative pain-alleviating agent” [<xref rid="B216-marinedrugs-18-00005" ref-type="bibr">216</xref>].</p><p>The neuroprotective activity of marine compounds (<bold>196</bold>, <bold>197</bold>, <bold>205</bold>, <bold>206</bold>, <bold>211</bold>) was reported in five studies. Wu and colleagues observed that the novel (Z)-7,4′-dimethoxy-6-hydroxy-aurone-4-O-<italic>β</italic>-glucopyranoside (<bold>196</bold>) isolated from the endophytic fungus <italic>Penicillium citrinum</italic> of the mangrove <italic>Bruguiera gymnorrhyza</italic> derivative decreased 1-methyl-4-phenylpyridium-induced neurotoxicity in rat pheochromocytoma PC12 cells in vitro by a mechanism that elevated mitochondrial membrane potential, decreased DNA fragmentation, and inhibited apoptosis [<xref rid="B212-marinedrugs-18-00005" ref-type="bibr">212</xref>]. Hjornevik and colleagues completed an extensive in vitro “neurotoxicological” study with the marine algal toxin azaspiracid-1 (<bold>197</bold>) and observed rat PC12 cells’ differentiation-related morphological changes associated with the expression of the PC12-associated neuronal differentiation marker peripherin on neurite-like processes, suggesting this molecule “triggers a differentiation process” [<xref rid="B213-marinedrugs-18-00005" ref-type="bibr">213</xref>]. Yamagishi and colleagues explored the structure–activity relationship of LLG-3 (<bold>205</bold>), a ganglioside isolated from the starfish <italic>Linchia laevigata</italic>, and discovered that the methyl group at C8 of the terminal sialic acid residue was of critical significance for neuritogenic activity. Furthermore, detailed signaling studies revealed the “activation of mitogen-activated protein kinase signaling pathway” [<xref rid="B221-marinedrugs-18-00005" ref-type="bibr">221</xref>]. Cassiano and colleagues, using chemical proteomics, noted that the terpenoid heteronemin (<bold>206</bold>), isolated from the marine sponge <italic>Hyrtios</italic> sp., targeted TDP-43, a major component of inclusions that characterize amyotrophic lateral sclerosis and front-temporal lobar degeneration, by lowering its affinity “towards nucleic acids”, and thus becoming a “relevant chemical tool in the study of TDP-43 related processes” [<xref rid="B222-marinedrugs-18-00005" ref-type="bibr">222</xref>]. Shimizu and colleagues provided the “first report” that the pro-electrophilic sesquiterpene zonarol (<bold>211</bold>), isolated from the Japanese brown alga <italic>Dictyopteris undulata</italic>, provided neuroprotection by activating the nuclear factor (erythroid-derived-2)-like 2/antioxidant responsive element Nrf2/ARE pathway, inducing phase-2 enzymes and providing oxidative stress protection to cerebrocortical neurons in vitro, concluding that the compound “represents a lead compound for the treatment of chronic neurodegenerative diseases associated with oxidative stress” [<xref rid="B228-marinedrugs-18-00005" ref-type="bibr">228</xref>].</p><p>As shown in <xref rid="marinedrugs-18-00005-t002" ref-type="table">Table 2</xref>, three marine compounds were shown to modulate other molecular targets, that is, γ-aminobutyric acid (GABA) receptor (<bold>209</bold>), and the acetylcholinesterase (<bold>204</bold>) and butyrylcholinesterase enzyme (<bold>10</bold>). Lee and colleagues discovered that the pigment echinochrome A (<bold>204</bold>), isolated from the sea urchin <italic>Scaphechinus,</italic> inhibited acetylcholinesterase (IC<sub>50</sub> = 16.4 µM) by an irreversible and uncompetitive mechanism that might be useful in “treating acetylcholine-limited diseases”, such as Alzheimer’s disease and “other forms of dementia” [<xref rid="B220-marinedrugs-18-00005" ref-type="bibr">220</xref>]. Eltahawy and colleagues isolated of a new ceramide (<bold>209</bold>) from the Red sea soft coral <italic>Sarcophyton auritum,</italic> which demonstrated antiepileptic activity in vivo with a central nervous system depressing mechanism that appeared to involve “GABA receptor modulation rather than serotonin receptor inhibition” [<xref rid="B226-marinedrugs-18-00005" ref-type="bibr">226</xref>]. Choi and colleagues reported that the polyphenol phlorofucofuroeckol-A (<bold>10</bold>), isolated from the Korean brown alga <italic>Ecklonia cava</italic>, potently inhibited butyrylcholinesterase, a novel target for Alzheimer’s disease, suggesting that “phlorotannins … to be very promising medicinal compounds” [<xref rid="B225-marinedrugs-18-00005" ref-type="bibr">225</xref>].</p><p>In contrast to the marine compounds affecting the nervous system with investigated mechanisms of action discussed above, and as shown in <xref rid="marinedrugs-18-00005-t002" ref-type="table">Table 2</xref>, for marine compounds (<bold>120</bold>, <bold>121</bold>, <bold>212</bold>-<bold>218</bold>), only an IC<sub>50</sub> was reported, but the molecular mechanism of action of these compounds remained undetermined at the time of publication: an Australian marine-sponge <italic>Aplysinella</italic> sp.-derived aplysinellamide-1 (<bold>212</bold>) [<xref rid="B229-marinedrugs-18-00005" ref-type="bibr">229</xref>], the novel lactones territrem D, and arisugacin A (<bold>120, 121</bold>) from a fungus <italic>Aspergillus terreus</italic> SCSGAF0162 derived from a South China sea gorgonian <italic>Echinogorgia aurantiaca</italic> [<xref rid="B115-marinedrugs-18-00005" ref-type="bibr">115</xref>]; an Indian marine cone snail <italic>Conus araneosus</italic> ar3j peptide (<bold>213</bold>) [<xref rid="B230-marinedrugs-18-00005" ref-type="bibr">230</xref>]; a new steroid (<bold>214</bold>) from a fungus <italic>Dichotomomyces cejpii</italic> isolated from an Australian marine sponge <italic>Callyspongia</italic> cf. C. <italic>flammea</italic> [<xref rid="B231-marinedrugs-18-00005" ref-type="bibr">231</xref>]; a novel genuanine (<bold>215</bold>) isolated from Cape Verde marine cone snail <italic>Conus genuanus</italic> [<xref rid="B232-marinedrugs-18-00005" ref-type="bibr">232</xref>]; a bromotyrosine alkaloid homoaerothionin (<bold>216</bold>) isolated from the Thai sponge <italic>Acanthodendrilla</italic> sp. [<xref rid="B233-marinedrugs-18-00005" ref-type="bibr">233</xref>]; a new alkyl amide mooreamide A (<bold>217</bold>) from the Papua New Guinean marine cyanobacterium <italic>Moorea bouillonii</italic> [<xref rid="B234-marinedrugs-18-00005" ref-type="bibr">234</xref>]; and a hydroxyoctaprenyl 1′,4′-hydroquinone (<bold>218</bold>) isolated from the Italian marine sponge <italic>Sarcotragus spinosulus</italic> [<xref rid="B235-marinedrugs-18-00005" ref-type="bibr">235</xref>].</p></sec></sec><sec id="sec4-marinedrugs-18-00005"><title>4. Marine Compounds with Miscellaneous Mechanisms of Action</title><p>The 2014–2015 preclinical pharmacology of 83 marine compounds (<bold>219</bold>–<bold>300</bold>) with miscellaneous mechanisms of action is shown in <xref rid="marinedrugs-18-00005-t003" ref-type="table">Table 3</xref>, with their corresponding structures presented in <xref ref-type="fig" rid="marinedrugs-18-00005-f003">Figure 3</xref>. Because, at the time of publication, a comprehensive pharmacological characterization of these compounds remained unavailable, their assignment to a particular drug class will probably require further investigation.</p><p>As reported in the peer-reviewed literature, <xref rid="marinedrugs-18-00005-t003" ref-type="table">Table 3</xref> presents the pharmacological activity, an IC<sub>50</sub>, and a molecular mechanism of action of the following marine natural compounds: sea anemone <italic>Aiptasia diaphana</italic> toxic peptide AdE-1 (<bold>219</bold>) [<xref rid="B236-marinedrugs-18-00005" ref-type="bibr">236</xref>]; sponge alkaloid aaptamine (<bold>220</bold>) [<xref rid="B237-marinedrugs-18-00005" ref-type="bibr">237</xref>]; dinoflagellate <italic>Amphidinium</italic> sp. polyketide amphirionin-4 (<bold>221</bold>) [<xref rid="B238-marinedrugs-18-00005" ref-type="bibr">238</xref>]; algal terpenoid astaxanthin (<bold>145</bold>) [<xref rid="B239-marinedrugs-18-00005" ref-type="bibr">239</xref>]; sponge alkaloids bastadins 6 and 16 (<bold>222, 223</bold>) [<xref rid="B240-marinedrugs-18-00005" ref-type="bibr">240</xref>]; brown alga <italic>Eisenia bicyclis</italic> polyketide 6,6-bieckol (<bold>224</bold>) [<xref rid="B241-marinedrugs-18-00005" ref-type="bibr">241</xref>]; <italic>Streptomyces</italic> sp. strain CNH-287 alkaloid (-)-chlorizidine A (<bold>225</bold>) [<xref rid="B242-marinedrugs-18-00005" ref-type="bibr">242</xref>]; soft coral <italic>Cladiella australis</italic> dihydroaustrasulfone alcohol (<bold>226</bold>) [<xref rid="B243-marinedrugs-18-00005" ref-type="bibr">243</xref>,<xref rid="B244-marinedrugs-18-00005" ref-type="bibr">244</xref>]; edible brown alga <italic>Ishige okamurae</italic> terpenoid diphlorethohydroxycarmalol (<bold>227</bold>) [<xref rid="B245-marinedrugs-18-00005" ref-type="bibr">245</xref>]; sea urchin <italic>Scaphechinus mirabilis</italic> alkaloid echinochrome A (<bold>204</bold>) [<xref rid="B246-marinedrugs-18-00005" ref-type="bibr">246</xref>,<xref rid="B247-marinedrugs-18-00005" ref-type="bibr">247</xref>]; brown alga <italic>Ecklonia stolonifera</italic> polyketide eckol (<bold>228</bold>) [<xref rid="B248-marinedrugs-18-00005" ref-type="bibr">248</xref>]; sponge derived fungus <italic>Dichotomomyces cejpii</italic> terpenoid emindole SB (<bold>229</bold>) [<xref rid="B249-marinedrugs-18-00005" ref-type="bibr">249</xref>]; Arctic <italic>Streptomyces nitrosporeus</italic> YBH10-5 farnesylquinone (<bold>230</bold>) [<xref rid="B250-marinedrugs-18-00005" ref-type="bibr">250</xref>]; fungus <italic>Stachybotrys longispora</italic> FG216 pyrano indolone alkaloid fibrinolytic compound 1 (<bold>231</bold>) [<xref rid="B251-marinedrugs-18-00005" ref-type="bibr">251</xref>]; fungus <italic>Paecilomyces formosus</italic> formosusin A (<bold>232</bold>) [<xref rid="B252-marinedrugs-18-00005" ref-type="bibr">252</xref>]; brown alga <italic>Ecklonia cava</italic> phlorotannin fucodiphlorethol G (<bold>233</bold>) [<xref rid="B253-marinedrugs-18-00005" ref-type="bibr">253</xref>]; green alga <italic>Spirogyra</italic> sp. polyphenol gallic acid (<bold>234</bold>) [<xref rid="B254-marinedrugs-18-00005" ref-type="bibr">254</xref>]; cyanobacterium <italic>Schizothrix</italic> sp. gallinamide A (<bold>235</bold>) [<xref rid="B255-marinedrugs-18-00005" ref-type="bibr">255</xref>]; sponge <italic>Stylissa aff. carteri</italic> girolline (<bold>236</bold>) [<xref rid="B256-marinedrugs-18-00005" ref-type="bibr">256</xref>]; sponge <italic>Spongionella</italic> sp. terpenoids gracilins H, A, and L (<bold>237–239</bold>) [<xref rid="B257-marinedrugs-18-00005" ref-type="bibr">257</xref>]; new anemone <italic>Heteractis crispa</italic> Kunitz-type polypeptides HCRG1 and HCRG2 (<bold>240, 241</bold>) [<xref rid="B258-marinedrugs-18-00005" ref-type="bibr">258</xref>]; new sponge <italic>Hyrtios</italic> sp. sesterterpenoid 2 (<bold>242</bold>) [<xref rid="B259-marinedrugs-18-00005" ref-type="bibr">259</xref>]; sponge <italic>Ircinia ramose</italic> irciniastatin A (<bold>243</bold>) [<xref rid="B260-marinedrugs-18-00005" ref-type="bibr">260</xref>]; ascidian <italic>Eudistoma</italic> cf. <italic>rigida</italic> polyketide lejimalide C (<bold>244</bold>) [<xref rid="B261-marinedrugs-18-00005" ref-type="bibr">261</xref>]; red alga <italic>Laurencia brongniartii</italic> brominated indole (<bold>245</bold>) [<xref rid="B262-marinedrugs-18-00005" ref-type="bibr">262</xref>]; sponge <italic>Neopetrosia</italic> sp. pyridine nucleoside neopetroside A (<bold>246</bold>) [<xref rid="B263-marinedrugs-18-00005" ref-type="bibr">263</xref>]; edible brown alga <italic>Ecklonia stolonifera</italic> phlorotannin phlorofucofuroeckol-A (<bold>10</bold>) [<xref rid="B264-marinedrugs-18-00005" ref-type="bibr">264</xref>]; sponge <italic>Theonella swinhoei</italic> peptide polytheonamide B (<bold>247</bold>) [<xref rid="B265-marinedrugs-18-00005" ref-type="bibr">265</xref>]; green alga <italic>Codium fragile</italic> terpenoid siphonaxanthin (<bold>248</bold>) [<xref rid="B266-marinedrugs-18-00005" ref-type="bibr">266</xref>]; deep-sea derived fungus <italic>Spiromastix</italic> sp. MCCC 3A00308 spiromastixones J and L (<bold>57, 249</bold>) [<xref rid="B267-marinedrugs-18-00005" ref-type="bibr">267</xref>]; bacteria <italic>Thalassospira</italic> sp. CNJ328 and <italic>Tistrella bauzanensis</italic> TIO7329 thalassospiramide C (<bold>250</bold>) [<xref rid="B268-marinedrugs-18-00005" ref-type="bibr">268</xref>]; mangrove fungus <italic>Xylaria</italic> sp. xyloketal B (<bold>251</bold>) [<xref rid="B269-marinedrugs-18-00005" ref-type="bibr">269</xref>,<xref rid="B270-marinedrugs-18-00005" ref-type="bibr">270</xref>]; and sponge <italic>Xestospongia testudinaria</italic> brominated polyunsaturated lipid (<bold>252</bold>) [<xref rid="B271-marinedrugs-18-00005" ref-type="bibr">271</xref>].</p><p>Also consolidated in <xref rid="marinedrugs-18-00005-t003" ref-type="table">Table 3</xref> is the pharmacological activity (IC<sub>50</sub> for enzyme or receptor inhibition) of marine-derived compounds (<bold>253</bold>–<bold>300</bold>), but the mechanism of action remained undetermined at the time of publication: a dinoflagellate <italic>Dinophysis acuminate</italic> new polyether macrolide acuminolide A (<bold>253</bold>) [<xref rid="B272-marinedrugs-18-00005" ref-type="bibr">272</xref>]; fungus <italic>Alternaria alternata</italic> alternariol derivatives (<bold>255</bold>–<bold>257</bold>) [<xref rid="B136-marinedrugs-18-00005" ref-type="bibr">136</xref>]; bacterium <italic>Streptomyces</italic> sp. linear peptide ahpatinin Ac (<bold>254</bold>) [<xref rid="B273-marinedrugs-18-00005" ref-type="bibr">273</xref>]; ascidian <italic>Aplidium</italic> sp. new dipeptide apliamide D (<bold>258</bold>) [<xref rid="B274-marinedrugs-18-00005" ref-type="bibr">274</xref>]; fungi <italic>Penicillium thomii</italic> and <italic>P. lividum</italic> new meroterpenoids austalides 4 and 9 (<bold>259, 260</bold>) [<xref rid="B275-marinedrugs-18-00005" ref-type="bibr">275</xref>]; <italic>Streptomyces axinellae</italic> axinelline A (<bold>261</bold>) [<xref rid="B276-marinedrugs-18-00005" ref-type="bibr">276</xref>]; dinoflagellate <italic>Karenia brevisulcata</italic> polyether brevisulcatic acid-4 (<bold>262</bold>) [<xref rid="B277-marinedrugs-18-00005" ref-type="bibr">277</xref>]; green alga <italic>Caulerpa racemose</italic> 4′,5′–dehydrodiodictyonema A (<bold>263</bold>) [<xref rid="B278-marinedrugs-18-00005" ref-type="bibr">278</xref>]; sponge <italic>Dactylospongia metachromia</italic> sesquiterpenes nakijiquinone N (<bold>264</bold>), nakijinol C (<bold>266</bold>), and known analog 18-hydroxy-5-<italic>epi</italic>-hyrtiophenol (<bold>265</bold>) [<xref rid="B279-marinedrugs-18-00005" ref-type="bibr">279</xref>]; ascidian <italic>Didemnum</italic> sp. spiroketals didemnaketals D and E (<bold>267, 268</bold>) [<xref rid="B280-marinedrugs-18-00005" ref-type="bibr">280</xref>]; sponge <italic>Dysidea avara</italic> sesquiterpene dysiquinol D (<bold>269</bold>) [<xref rid="B281-marinedrugs-18-00005" ref-type="bibr">281</xref>]; brown alga <italic>Laminaria japo</italic>nica terpenoid fucoxanthin (<bold>134</bold>) [<xref rid="B282-marinedrugs-18-00005" ref-type="bibr">282</xref>]; sponge <italic>Xestospongia testudinaria</italic> halenaquinol sulfate (<bold>270</bold>) [<xref rid="B283-marinedrugs-18-00005" ref-type="bibr">283</xref>]; sponge <italic>Xetospongia</italic> sp. halenaquinone derivative, 1-hydroxyethylhalenaquinone (<bold>271</bold>) [<xref rid="B284-marinedrugs-18-00005" ref-type="bibr">284</xref>]; sponge <italic>Stylissa massa</italic> and <italic>S. flabelliformis</italic> bromopyrrole alkaloids (<bold>272</bold>–<bold>274</bold>) [<xref rid="B285-marinedrugs-18-00005" ref-type="bibr">285</xref>]; sponge <italic>Callyspongia</italic> sp. hymenialdisine (<bold>275</bold>) [<xref rid="B286-marinedrugs-18-00005" ref-type="bibr">286</xref>]; sponge <italic>Hyattella</italic> sp. hyattellactone A (<bold>276</bold>) [<xref rid="B287-marinedrugs-18-00005" ref-type="bibr">287</xref>]; sponge <italic>Hippospongia lachne</italic> sesterterpene hippolide derivative (<bold>277</bold>) [<xref rid="B288-marinedrugs-18-00005" ref-type="bibr">288</xref>]; sponge <italic>Suberea ianthelliformis</italic> ianthelliformisamines A, B, and C (<bold>278, 7, 8</bold>) [<xref rid="B289-marinedrugs-18-00005" ref-type="bibr">289</xref>]; sponge <italic>Plakortis</italic> cfr. <italic>lita</italic> sterols incisterols A5 and A6 (<bold>279, 280</bold>) [<xref rid="B290-marinedrugs-18-00005" ref-type="bibr">290</xref>]; soft coral <italic>Lobophytum crissum</italic> cembranoid diterpene 2,16:7<italic>S</italic>,8<italic>S</italic>,-diepoxy 1,3,11,15-cembratetraene (<bold>281</bold>) [<xref rid="B291-marinedrugs-18-00005" ref-type="bibr">291</xref>]; red alga <italic>Laurencia okamurai</italic> laurene-type sesquiterpenoid laurokamurane A (<bold>282</bold>) [<xref rid="B292-marinedrugs-18-00005" ref-type="bibr">292</xref>]; gorgonian <italic>Echinogorgia pseudossapo</italic> alkaloid malonganenone L (<bold>283</bold>) [<xref rid="B293-marinedrugs-18-00005" ref-type="bibr">293</xref>]; fungus <italic>Hansfordia sinuosae</italic> sesquiterpenoid punctaporonin K (<bold>284</bold>) [<xref rid="B294-marinedrugs-18-00005" ref-type="bibr">294</xref>]; fungus <italic>Aspergillus versicolor</italic> ZLN-60 cyclic peptide psychrophilin G (<bold>285</bold>) [<xref rid="B295-marinedrugs-18-00005" ref-type="bibr">295</xref>]; green alga <italic>Caulerpa racemosa</italic> bisindole alklaloid racemosin C (<bold>286</bold>) [<xref rid="B296-marinedrugs-18-00005" ref-type="bibr">296</xref>]; soft coral <italic>Sarcophyton ehrenbergi</italic> prostaglandin derivative sarcoehrendin B (<bold>287</bold>) [<xref rid="B297-marinedrugs-18-00005" ref-type="bibr">297</xref>]; soft coral <italic>Sarcophyton trocheliophorum</italic> Marenzeller diterpene sarsolilide A (<bold>288</bold>) [<xref rid="B298-marinedrugs-18-00005" ref-type="bibr">298</xref>]; fungus <italic>Stachybotry</italic> sp. HH1 ZSDS1F1-2 xanthone derivative stachybogrisephenone B (<bold>289</bold>) [<xref rid="B299-marinedrugs-18-00005" ref-type="bibr">299</xref>]; brown alga <italic>Sargassum thunbergii</italic> alkapolyene 1 (<bold>290</bold>) [<xref rid="B300-marinedrugs-18-00005" ref-type="bibr">300</xref>]; red alga <italic>Palmaria palmata</italic> mycosporine-like amino acid shinorine (<bold>291</bold>) [<xref rid="B301-marinedrugs-18-00005" ref-type="bibr">301</xref>]; soft coral <italic>Sinularia</italic> sp. cyclopentenone sinularone D (<bold>292</bold>) [<xref rid="B302-marinedrugs-18-00005" ref-type="bibr">302</xref>]; fungus <italic>Stachybotrys chartarum N</italic>-(2-benzenepropanoic acid) stachybotrylactam (<bold>293</bold>) [<xref rid="B303-marinedrugs-18-00005" ref-type="bibr">303</xref>]; sponge <italic>Petrosia corticata</italic> meroditerpenoids strongylophorine -13/-14 (<bold>294</bold>) [<xref rid="B304-marinedrugs-18-00005" ref-type="bibr">304</xref>]; sponge <italic>Theonella swinhoei</italic> steroid swinhoeisterol A (<bold>295</bold>) [<xref rid="B305-marinedrugs-18-00005" ref-type="bibr">305</xref>]; brown alga <italic>Sargassum thunbergii</italic> thunberol (<bold>296</bold>) [<xref rid="B306-marinedrugs-18-00005" ref-type="bibr">306</xref>]; sponge <italic>Xestospongia vansoesti</italic> meroterpenoid xestosaprol O (<bold>297</bold>) [<xref rid="B307-marinedrugs-18-00005" ref-type="bibr">307</xref>]; sponge <italic>Monanchora pulchra</italic> bisguanidine alkaloid urupocidin A (<bold>298</bold>) [<xref rid="B308-marinedrugs-18-00005" ref-type="bibr">308</xref>]; sponge <italic>Luffariella variabilis</italic> β-carboline alkaloid variabine B (<bold>299</bold>) [<xref rid="B309-marinedrugs-18-00005" ref-type="bibr">309</xref>]; and cyanobacterium <italic>Leptolyngbya</italic> sp. yoshinone A (<bold>300</bold>) [<xref rid="B310-marinedrugs-18-00005" ref-type="bibr">310</xref>].</p></sec><sec id="sec5-marinedrugs-18-00005"><title>5. Reviews on Marine Pharmacology and Pharmaceuticals</title><p>In 2014–2015, several reviews covered general and/or specific areas of marine preclinical pharmacology: (a) <bold><italic>Marine pharmacology and marine pharmaceuticals:</italic></bold> new marine natural products and relevant biological activities published in 2014 and 2015 [<xref rid="B311-marinedrugs-18-00005" ref-type="bibr">311</xref>,<xref rid="B312-marinedrugs-18-00005" ref-type="bibr">312</xref>]; marine peptides, bioactivities and applications [<xref rid="B313-marinedrugs-18-00005" ref-type="bibr">313</xref>]; bioactive terpenes from marine-derived fungi [<xref rid="B314-marinedrugs-18-00005" ref-type="bibr">314</xref>]; bioactive marine natural products from actinobacteria with unique chemical structures [<xref rid="B315-marinedrugs-18-00005" ref-type="bibr">315</xref>]; Baltic cyanobacteria as a source of biologically active compounds [<xref rid="B316-marinedrugs-18-00005" ref-type="bibr">316</xref>]; biological targets of marine cyanobacteria natural products [<xref rid="B317-marinedrugs-18-00005" ref-type="bibr">317</xref>]; marine mussels as a source for bioactive compounds for human health [<xref rid="B318-marinedrugs-18-00005" ref-type="bibr">318</xref>]; pharmacological potential of cephalopod ink in drug discovery [<xref rid="B319-marinedrugs-18-00005" ref-type="bibr">319</xref>]; pharmacologically active Brazilian octocorals [<xref rid="B320-marinedrugs-18-00005" ref-type="bibr">320</xref>]; bioactive natural products isolated from marine microorganisms from Brazil [<xref rid="B321-marinedrugs-18-00005" ref-type="bibr">321</xref>]; statistical analysis of marine natural product bioactivity from 1985–2012 [<xref rid="B322-marinedrugs-18-00005" ref-type="bibr">322</xref>]; metagenomics and marine natural products drug discovery [<xref rid="B323-marinedrugs-18-00005" ref-type="bibr">323</xref>]; new horizons for selected marine natural products as drug leads [<xref rid="B324-marinedrugs-18-00005" ref-type="bibr">324</xref>]; marine-sourced agents in clinical and late preclinical development [<xref rid="B325-marinedrugs-18-00005" ref-type="bibr">325</xref>]; the global marine pharmaceutical pipeline in 2019: approved compounds and those in Phase I, II, and III of clinical development <uri xlink:href="https://www.midwestern.edu/departments/marinepharmacology.xml">https://www.midwestern.edu/departments/marinepharmacology.xml</uri>. (b) <bold><italic>Antimicrobial marine pharmacology</italic></bold><italic>:</italic> biophysical properties of anti-lipopolysaccharide antimicrobial peptides isolated from marine fish [<xref rid="B326-marinedrugs-18-00005" ref-type="bibr">326</xref>]; marine peptides and their anti-microbial activities [<xref rid="B327-marinedrugs-18-00005" ref-type="bibr">327</xref>]; marine membrane-active peptides as antimicrobials [<xref rid="B328-marinedrugs-18-00005" ref-type="bibr">328</xref>]; marine fungi antibacterial compounds [<xref rid="B329-marinedrugs-18-00005" ref-type="bibr">329</xref>]. (c) <bold><italic>Antiviral marine pharmacology</italic></bold>: marine natural products with antiviral potential [<xref rid="B330-marinedrugs-18-00005" ref-type="bibr">330</xref>]; antiviral activity in marine fungi-derived natural products [<xref rid="B331-marinedrugs-18-00005" ref-type="bibr">331</xref>]. (d) <bold><italic>Antiprotozoal and antimalarial marine pharmacology</italic></bold><italic>:</italic> antiprotozoal activity in marine natural products isolated from marine algae [<xref rid="B332-marinedrugs-18-00005" ref-type="bibr">332</xref>]; marine indole alkaloids as potential leads for antiprotozoal drugs [<xref rid="B333-marinedrugs-18-00005" ref-type="bibr">333</xref>]; antimalarial potency of the manzamine β-carboline alkaloids [<xref rid="B334-marinedrugs-18-00005" ref-type="bibr">334</xref>]. (e) <bold><italic>Immuno- and anti-inflammatory marine pharmacology</italic></bold><italic>:</italic> marine diterpenoids as potential anti-inflammatory agents [<xref rid="B335-marinedrugs-18-00005" ref-type="bibr">335</xref>]; microalgae bioactive compounds for inflammation and cancer [<xref rid="B336-marinedrugs-18-00005" ref-type="bibr">336</xref>]. (f) <bold><italic>Cardiovascular and antidiabetic marine pharmacology</italic></bold>: marine-derived natural products as a source of cardiovascular protective agents [<xref rid="B337-marinedrugs-18-00005" ref-type="bibr">337</xref>]; antioxidant phlorotannins derived from marine algae [<xref rid="B338-marinedrugs-18-00005" ref-type="bibr">338</xref>]; antioxidant carotenoids isolated from marine Gram-positive bacteria [<xref rid="B339-marinedrugs-18-00005" ref-type="bibr">339</xref>]; brown alga-derived fucoxanthin for diabetes therapy [<xref rid="B340-marinedrugs-18-00005" ref-type="bibr">340</xref>]; bioactive compounds from seaweed for diabetes [<xref rid="B341-marinedrugs-18-00005" ref-type="bibr">341</xref>]. (g) <bold><italic>Nervous system marine pharmacology</italic></bold><italic>:</italic> astaxanthin as a potential neuroprotective agent [<xref rid="B342-marinedrugs-18-00005" ref-type="bibr">342</xref>]; origin, distribution, toxicity, and therapeutic uses of the marine neurotoxin tetrodotoxin [<xref rid="B343-marinedrugs-18-00005" ref-type="bibr">343</xref>]; marine natural products with neuroprotective activity [<xref rid="B344-marinedrugs-18-00005" ref-type="bibr">344</xref>]; marine-terpenoid gracilins as promising compounds for Alzheimer’s disease [<xref rid="B345-marinedrugs-18-00005" ref-type="bibr">345</xref>]; new marine drugs for Alzheimer’s disease treatment [<xref rid="B346-marinedrugs-18-00005" ref-type="bibr">346</xref>]. (h) <bold><italic>Miscellaneous molecular targets and uses</italic></bold>: matrix metalloproteinase inhibitors isolated from edible marine algae [<xref rid="B347-marinedrugs-18-00005" ref-type="bibr">347</xref>]; marine natural products that targeting apoptosis signaling pathways [<xref rid="B348-marinedrugs-18-00005" ref-type="bibr">348</xref>]; scytonemin and emerging biomedical applications [<xref rid="B349-marinedrugs-18-00005" ref-type="bibr">349</xref>]; antiobesity effects of the carotenoid fucoxanthin [<xref rid="B350-marinedrugs-18-00005" ref-type="bibr">350</xref>]; therapeutic potential of astaxanthin [<xref rid="B351-marinedrugs-18-00005" ref-type="bibr">351</xref>]; pharmacological properties of marine coumarins [<xref rid="B352-marinedrugs-18-00005" ref-type="bibr">352</xref>].</p></sec><sec sec-type="conclusions" id="sec6-marinedrugs-18-00005"><title>6. Conclusions</title><p>The current marine pharmacology 2014–2015 review is a sequel to the marine <italic>preclinical</italic> pharmacology pipeline review series initiated in 1998 [<xref rid="B1-marinedrugs-18-00005" ref-type="bibr">1</xref>,<xref rid="B2-marinedrugs-18-00005" ref-type="bibr">2</xref>,<xref rid="B3-marinedrugs-18-00005" ref-type="bibr">3</xref>,<xref rid="B4-marinedrugs-18-00005" ref-type="bibr">4</xref>,<xref rid="B5-marinedrugs-18-00005" ref-type="bibr">5</xref>,<xref rid="B6-marinedrugs-18-00005" ref-type="bibr">6</xref>,<xref rid="B7-marinedrugs-18-00005" ref-type="bibr">7</xref>,<xref rid="B8-marinedrugs-18-00005" ref-type="bibr">8</xref>,<xref rid="B9-marinedrugs-18-00005" ref-type="bibr">9</xref>], and consolidates the peer-reviewed preclinical marine pharmacological literature published during 2014–2015. The global preclinical marine pharmacology research involved chemists and pharmacologists from 43 countries, namely, Australia, Austria, Bangladesh, Belgium, Brazil, Canada, China, Colombia, Costa Rica, Cuba, Denmark, Egypt, Finland, France, French Polynesia, Germany, Hungary, India, Indonesia, Ireland, Israel, Italy, Japan, Malaysia, Mexico, the Netherlands, New Zealand, Norway, Papua New Guinea, Portugal, Russian Federation, Saudi Arabia, Singapore, South Africa, South Korea, Spain, Sri Lanka, Switzerland, Taiwan, Thailand, United Kingdom, Vietnam, and the United States. Thus, during 2014–2015, the marine <italic>preclinical</italic> pharmaceutical pipeline continued to provide novel pharmacology that provided novel leads for the marine <italic>clinical</italic> pharmaceutical pipeline. As shown at the global marine pharmaceutical pipeline website, <uri xlink:href="https://www.midwestern.edu/departments/marinepharmacology.xml">https://www.midwestern.edu/departments/marinepharmacology.xml</uri>, there are currently 9 approved marine-derived pharmaceuticals, and an additional 31 compounds are either in Phase I, II, and III of <italic>clinical</italic> pharmaceutical development. </p></sec></body><back><ack><title>Acknowledgments</title><p>We thank the contributions of Kelly Le, Pharm. D., and Jefferson Trieu, Pharm. D., both graduates from the Chicago College of Pharmacy, Midwestern University for marine pharmacology literature retrieval, and Colleen Bannon, Midwestern University Library, for Endnote database assistance. In particular, we wish to acknowledge Mary Hall’s tireless and careful review of the preclinical pharmacological data presented in 805 articles that were retrieved from the global marine pharmacology literature for the 2014–2015 period. We also thank the secretarial assistance of Victoria Sears and Laura Phelps from the Pharmacology Department, College of Graduate Studies. We gratefully acknowledge financial support from Midwestern University to A.M.S.M.; and NIH-SC1 Award (Grant 1SC1GM086271-01A1) of the University of Puerto Rico to A.D.R., and a grant from Regione Campania-POR Campania FESR 2014/2020 “Combattere la resistenza tumorale: piattaforma integrata multidisciplinare per un approccio tecnologico innovativo alle oncoterapie-Campania Oncoterapie” (Project N. B61G18000470007) to O.T.S. 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xlink:href="marinedrugs-18-00005-g001h"></graphic><graphic xlink:href="marinedrugs-18-00005-g001i"></graphic><graphic xlink:href="marinedrugs-18-00005-g001j"></graphic><graphic xlink:href="marinedrugs-18-00005-g001k"></graphic></fig><fig id="marinedrugs-18-00005-f002" orientation="portrait" position="float"><label>Figure 2</label><caption><p>Marine pharmacology in 2014–2015: marine compounds with antidiabetic and anti-inflammatory activity, and affecting the immune and nervous system.</p></caption><graphic xlink:href="marinedrugs-18-00005-g002a"></graphic><graphic xlink:href="marinedrugs-18-00005-g002b"></graphic><graphic xlink:href="marinedrugs-18-00005-g002c"></graphic><graphic xlink:href="marinedrugs-18-00005-g002d"></graphic><graphic xlink:href="marinedrugs-18-00005-g002e"></graphic><graphic xlink:href="marinedrugs-18-00005-g002f"></graphic><graphic xlink:href="marinedrugs-18-00005-g002g"></graphic></fig><fig id="marinedrugs-18-00005-f003" orientation="portrait" position="float"><label>Figure 3</label><caption><p>Marine pharmacology in 2014–2015: marine compounds with miscellaneous mechanisms of action.</p></caption><graphic xlink:href="marinedrugs-18-00005-g003a"></graphic><graphic xlink:href="marinedrugs-18-00005-g003b"></graphic><graphic xlink:href="marinedrugs-18-00005-g003c"></graphic><graphic xlink:href="marinedrugs-18-00005-g003d"></graphic><graphic xlink:href="marinedrugs-18-00005-g003e"></graphic><graphic xlink:href="marinedrugs-18-00005-g003f"></graphic><graphic xlink:href="marinedrugs-18-00005-g003g"></graphic><graphic xlink:href="marinedrugs-18-00005-g003h"></graphic><graphic xlink:href="marinedrugs-18-00005-g003i"></graphic></fig><table-wrap id="marinedrugs-18-00005-t001" orientation="portrait" position="float"><object-id pub-id-type="pii">marinedrugs-18-00005-t001_Table 1</object-id><label>Table 1</label><caption><p>Marine pharmacology in 2014–2015: marine compounds with antibacterial, antifungal, antituberculosis, antiprotozoal, antiviral, and anthelmintic activities.</p></caption><table frame="hsides" rules="groups"><thead><tr><th align="left" valign="middle" style="border-top:solid thin;border-bottom:solid thin" rowspan="1" colspan="1">Drug Class</th><th align="left" valign="middle" style="border-top:solid thin;border-bottom:solid thin" rowspan="1" colspan="1">Compound/Organism <sup>a</sup></th><th align="left" valign="middle" style="border-top:solid thin;border-bottom:solid thin" rowspan="1" colspan="1">Chemistry</th><th align="left" valign="middle" style="border-top:solid thin;border-bottom:solid thin" rowspan="1" colspan="1">Pharmacologic Activity</th><th align="left" valign="middle" style="border-top:solid thin;border-bottom:solid thin" rowspan="1" colspan="1">IC<sub>50</sub><sup>b</sup></th><th align="left" valign="middle" style="border-top:solid thin;border-bottom:solid thin" rowspan="1" colspan="1">MMOA <sup>b</sup></th><th align="left" valign="middle" style="border-top:solid thin;border-bottom:solid thin" rowspan="1" colspan="1">Country <sup>c</sup></th><th align="left" valign="middle" style="border-top:solid thin;border-bottom:solid thin" rowspan="1" colspan="1">References</th></tr></thead><tbody><tr><td align="left" valign="middle" rowspan="1" colspan="1">Antibacterial</td><td align="left" valign="middle" rowspan="1" colspan="1">axinellamines A and B (<bold>1</bold>, <bold>2</bold>)/sponge</td><td align="left" valign="middle" rowspan="1" colspan="1">Alkaloid <sup>f</sup></td><td align="left" valign="middle" rowspan="1" colspan="1">Gram-positive and negative inhibition</td><td align="left" valign="middle" rowspan="1" colspan="1">0.5–32 μg/mL <sup>+</sup></td><td align="left" valign="middle" rowspan="1" colspan="1">Normal cellular division inhibition</td><td align="left" valign="middle" rowspan="1" colspan="1">USA</td><td align="left" valign="middle" rowspan="1" colspan="1">[<xref rid="B24-marinedrugs-18-00005" ref-type="bibr">24</xref>]</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">Antibacterial</td><td align="left" valign="middle" rowspan="1" colspan="1">buanmycin (<bold>3</bold>)/bacterium</td><td align="left" valign="middle" rowspan="1" colspan="1">Polyketide <sup>d</sup></td><td align="left" valign="middle" rowspan="1" colspan="1"><italic>S. enterica</italic> inhibition</td><td align="left" valign="middle" rowspan="1" colspan="1">0.7 μM <sup>+</sup></td><td align="left" valign="middle" rowspan="1" colspan="1">Sortase A inhibition</td><td align="left" valign="middle" rowspan="1" colspan="1">S. KOR</td><td align="left" valign="middle" rowspan="1" colspan="1">[<xref rid="B25-marinedrugs-18-00005" ref-type="bibr">25</xref>]</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">Antibacterial</td><td align="left" valign="middle" rowspan="1" colspan="1">cathelicidin (<bold>4</bold>)/sea snake</td><td align="left" valign="middle" rowspan="1" colspan="1">Peptide <sup>f</sup></td><td align="left" valign="middle" rowspan="1" colspan="1">Gram-positive and negative inhibition</td><td align="left" valign="middle" rowspan="1" colspan="1">0.16–20.7 μg/mL <sup>+</sup></td><td align="left" valign="middle" rowspan="1" colspan="1">Membrane morphology alteration</td><td align="left" valign="middle" rowspan="1" colspan="1">CHN</td><td align="left" valign="middle" rowspan="1" colspan="1">[<xref rid="B26-marinedrugs-18-00005" ref-type="bibr">26</xref>]</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">Antibacterial</td><td align="left" valign="middle" rowspan="1" colspan="1">clavanin A (<bold>5</bold>)/ascidian</td><td align="left" valign="middle" rowspan="1" colspan="1">Peptide <sup>f</sup></td><td align="left" valign="middle" rowspan="1" colspan="1"><italic>S. aureus</italic> and <italic>E. coli</italic> infection inhibition</td><td align="left" valign="middle" rowspan="1" colspan="1">10 mg/kg ***</td><td align="left" valign="middle" rowspan="1" colspan="1">IL-6 and TNF-α inhibition</td><td align="left" valign="middle" rowspan="1" colspan="1">BRA</td><td align="left" valign="middle" rowspan="1" colspan="1">[<xref rid="B27-marinedrugs-18-00005" ref-type="bibr">27</xref>]</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">Antibacterial</td><td align="left" valign="middle" rowspan="1" colspan="1">gelliusterol E (<bold>6</bold>)/sponge</td><td align="left" valign="middle" rowspan="1" colspan="1">Terpenoid <sup>e</sup></td><td align="left" valign="middle" rowspan="1" colspan="1"><italic>C. trachomatis</italic> inhibition</td><td align="left" valign="middle" rowspan="1" colspan="1">2.34 μM</td><td align="left" valign="middle" rowspan="1" colspan="1">OmpA protein inhibition</td><td align="left" valign="middle" rowspan="1" colspan="1">EGY, GBR</td><td align="left" valign="middle" rowspan="1" colspan="1">[<xref rid="B28-marinedrugs-18-00005" ref-type="bibr">28</xref>]</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">Antibacterial</td><td align="left" valign="middle" rowspan="1" colspan="1">ianthelliformisamimes B and C (<bold>7</bold>, <bold>8</bold>)/sponge</td><td align="left" valign="middle" rowspan="1" colspan="1">Alkaloid <sup>f</sup></td><td align="left" valign="middle" rowspan="1" colspan="1">Enhanced antibiotics against <italic>E. aerogenes, P. aeruginosa, K. Pneumoniae</italic> MDR strains in vitro </td><td align="left" valign="middle" rowspan="1" colspan="1">3.12–12.5 μM *</td><td align="left" valign="middle" rowspan="1" colspan="1">Enhancement of drug transporters</td><td align="left" valign="middle" rowspan="1" colspan="1">FRA</td><td align="left" valign="middle" rowspan="1" colspan="1">[<xref rid="B29-marinedrugs-18-00005" ref-type="bibr">29</xref>]</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">Antibacterial</td><td align="left" valign="middle" rowspan="1" colspan="1">pardaxin (<bold>9</bold>)/flatfish</td><td align="left" valign="middle" rowspan="1" colspan="1">Peptide <sup>f</sup></td><td align="left" valign="middle" rowspan="1" colspan="1"><italic>MR S. aureus</italic> inhibition <italic>in vivo</italic></td><td align="left" valign="middle" rowspan="1" colspan="1">8 mg/mL *</td><td align="left" valign="middle" rowspan="1" colspan="1">MCP-1, IL-6, and TNF-α inhibition</td><td align="left" valign="middle" rowspan="1" colspan="1">TWN</td><td align="left" valign="middle" rowspan="1" colspan="1">[<xref rid="B30-marinedrugs-18-00005" ref-type="bibr">30</xref>]</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">Antibacterial</td><td align="left" valign="middle" rowspan="1" colspan="1">phlorofucofuroeckol-A (<bold>10</bold>)/alga</td><td align="left" valign="middle" rowspan="1" colspan="1">Polyketide <sup>d</sup></td><td align="left" valign="middle" rowspan="1" colspan="1"><italic>MR S. aureus</italic> inhibition </td><td align="left" valign="middle" rowspan="1" colspan="1">32 μg/mL <sup>+</sup></td><td align="left" valign="middle" rowspan="1" colspan="1">PBP2a suppresion</td><td align="left" valign="middle" rowspan="1" colspan="1">S. KOR</td><td align="left" valign="middle" rowspan="1" colspan="1">[<xref rid="B31-marinedrugs-18-00005" ref-type="bibr">31</xref>]</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">Antibacterial</td><td align="left" valign="middle" rowspan="1" colspan="1">salinamide F (<bold>11</bold>)/bacterium</td><td align="left" valign="middle" rowspan="1" colspan="1">Peptide <sup>f</sup></td><td align="left" valign="middle" rowspan="1" colspan="1"><italic>E. coli</italic> inhibition</td><td align="left" valign="middle" rowspan="1" colspan="1">0.2 μg/mL <sup>+</sup></td><td align="left" valign="middle" rowspan="1" colspan="1">RNAP inhibition</td><td align="left" valign="middle" rowspan="1" colspan="1">USA</td><td align="left" valign="middle" rowspan="1" colspan="1">[<xref rid="B32-marinedrugs-18-00005" ref-type="bibr">32</xref>]</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">Antibacterial</td><td align="left" valign="middle" rowspan="1" colspan="1">piscidins (<bold>12</bold>, <bold>13</bold>)/fish</td><td align="left" valign="middle" rowspan="1" colspan="1">Peptide <sup>f</sup></td><td align="left" valign="middle" rowspan="1" colspan="1"><italic>K. pneumonia</italic> and <italic>A. baumannii</italic> inhibition <italic>in vitro</italic></td><td align="left" valign="middle" rowspan="1" colspan="1">1.5–3.1 μM <sup>+</sup></td><td align="left" valign="middle" rowspan="1" colspan="1">Undetermined</td><td align="left" valign="middle" rowspan="1" colspan="1">TWN</td><td align="left" valign="middle" rowspan="1" colspan="1">[<xref rid="B33-marinedrugs-18-00005" ref-type="bibr">33</xref>]</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">Antibacterial</td><td align="left" valign="middle" rowspan="1" colspan="1">adametizine A (<bold>14</bold>)/fungus</td><td align="left" valign="middle" rowspan="1" colspan="1">Terpenoid <sup>e</sup></td><td align="left" valign="middle" rowspan="1" colspan="1"><italic>S. aureus</italic> inhibition</td><td align="left" valign="middle" rowspan="1" colspan="1">8 μg/mL <sup>+</sup></td><td align="left" valign="middle" rowspan="1" colspan="1">Undetermined</td><td align="left" valign="middle" rowspan="1" colspan="1">CHN</td><td align="left" valign="middle" rowspan="1" colspan="1">[<xref rid="B34-marinedrugs-18-00005" ref-type="bibr">34</xref>]</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">Antibacterial</td><td align="left" valign="middle" rowspan="1" colspan="1">agelamadins A and B (<bold>15</bold>, <bold>16</bold>)/sponge</td><td align="left" valign="middle" rowspan="1" colspan="1">Alkaloid <sup>f</sup></td><td align="left" valign="middle" rowspan="1" colspan="1"><italic>M. luteus</italic> and <italic>C. neoformans</italic> inhibition</td><td align="left" valign="middle" rowspan="1" colspan="1">5–8 μg/mL <sup>+</sup></td><td align="left" valign="middle" rowspan="1" colspan="1">Undetermined</td><td align="left" valign="middle" rowspan="1" colspan="1">AUS, JPN</td><td align="left" valign="middle" rowspan="1" colspan="1">[<xref rid="B35-marinedrugs-18-00005" ref-type="bibr">35</xref>] </td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">Antibacterial</td><td align="left" valign="middle" rowspan="1" colspan="1"><italic>Aspergillus</italic> sp. butyrolactone (<bold>17</bold>)/fungus</td><td align="left" valign="middle" rowspan="1" colspan="1">Terpenoid <sup>e</sup></td><td align="left" valign="middle" rowspan="1" colspan="1"><italic>S. aureus</italic> and <italic>B. cereus</italic> inhibition</td><td align="left" valign="middle" rowspan="1" colspan="1">1.56 μM <sup>+</sup></td><td align="left" valign="middle" rowspan="1" colspan="1">Undetermined</td><td align="left" valign="middle" rowspan="1" colspan="1">CHN</td><td align="left" valign="middle" rowspan="1" colspan="1">[<xref rid="B36-marinedrugs-18-00005" ref-type="bibr">36</xref>]</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">Antibacterial</td><td align="left" valign="middle" rowspan="1" colspan="1">aszonapyrone A (<bold>18</bold>)/fungus</td><td align="left" valign="middle" rowspan="1" colspan="1">Terpenoid <sup>e</sup></td><td align="left" valign="middle" rowspan="1" colspan="1"><italic>S. aureus</italic> and <italic>B. subtilis</italic> inhibition</td><td align="left" valign="middle" rowspan="1" colspan="1">8 μg/mL <sup>+</sup></td><td align="left" valign="middle" rowspan="1" colspan="1">Undetermined</td><td align="left" valign="middle" rowspan="1" colspan="1">PRT, THAI</td><td align="left" valign="middle" rowspan="1" colspan="1">[<xref rid="B37-marinedrugs-18-00005" ref-type="bibr">37</xref>]</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">Antibacterial</td><td align="left" valign="middle" rowspan="1" colspan="1">austalide R (<bold>19</bold>)/fungus</td><td align="left" valign="middle" rowspan="1" colspan="1">Terpenoid <sup>e</sup></td><td align="left" valign="middle" rowspan="1" colspan="1">Marine bacteria inhibition</td><td align="left" valign="middle" rowspan="1" colspan="1">0.1 μg/mL <sup>+</sup></td><td align="left" valign="middle" rowspan="1" colspan="1">Undetermined</td><td align="left" valign="middle" rowspan="1" colspan="1">CHN, DEU, GBR</td><td align="left" valign="middle" rowspan="1" colspan="1">[<xref rid="B38-marinedrugs-18-00005" ref-type="bibr">38</xref>]</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">Antibacterial</td><td align="left" valign="middle" rowspan="1" colspan="1">citrifelin B (<bold>20</bold>)/fungus</td><td align="left" valign="middle" rowspan="1" colspan="1">Polyketide <sup>d</sup></td><td align="left" valign="middle" rowspan="1" colspan="1"><italic>S. aureus</italic> inhibition</td><td align="left" valign="middle" rowspan="1" colspan="1">4 μg/mL <sup>+</sup></td><td align="left" valign="middle" rowspan="1" colspan="1">Undetermined</td><td align="left" valign="middle" rowspan="1" colspan="1">CHN</td><td align="left" valign="middle" rowspan="1" colspan="1">[<xref rid="B39-marinedrugs-18-00005" ref-type="bibr">39</xref>]</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">Antibacterial</td><td align="left" valign="middle" rowspan="1" colspan="1">desmethylisaridin C1 (<bold>21</bold>)/fungus</td><td align="left" valign="middle" rowspan="1" colspan="1">Peptide <sup>f</sup></td><td align="left" valign="middle" rowspan="1" colspan="1"><italic>E. coli</italic> inhibition </td><td align="left" valign="middle" rowspan="1" colspan="1">8 μg/mL</td><td align="left" valign="middle" rowspan="1" colspan="1">Undetermined</td><td align="left" valign="middle" rowspan="1" colspan="1">CHN</td><td align="left" valign="middle" rowspan="1" colspan="1">[<xref rid="B40-marinedrugs-18-00005" ref-type="bibr">40</xref>]</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">Antibacterial</td><td align="left" valign="middle" rowspan="1" colspan="1"><italic>D. granulosa</italic> diphenyl ethers (<bold>22</bold>, <bold>23</bold>)/sponge</td><td align="left" valign="middle" rowspan="1" colspan="1">Polyketide <sup>d</sup></td><td align="left" valign="middle" rowspan="1" colspan="1">Gram-positive and negative inhibition</td><td align="left" valign="middle" rowspan="1" colspan="1">1–16 μg/mL <sup>+</sup></td><td align="left" valign="middle" rowspan="1" colspan="1">Undetermined</td><td align="left" valign="middle" rowspan="1" colspan="1">USA</td><td align="left" valign="middle" rowspan="1" colspan="1">[<xref rid="B41-marinedrugs-18-00005" ref-type="bibr">41</xref>]</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">Antibacterial</td><td align="left" valign="middle" rowspan="1" colspan="1">diaporthalasin (<bold>24</bold>) /fungus</td><td align="left" valign="middle" rowspan="1" colspan="1">Terpenoid <sup>e</sup></td><td align="left" valign="middle" rowspan="1" colspan="1">MR <italic>S. aureus</italic> inhibition</td><td align="left" valign="middle" rowspan="1" colspan="1">2 μg/mL <sup>+</sup></td><td align="left" valign="middle" rowspan="1" colspan="1">Undetermined</td><td align="left" valign="middle" rowspan="1" colspan="1">THAI</td><td align="left" valign="middle" rowspan="1" colspan="1">[<xref rid="B42-marinedrugs-18-00005" ref-type="bibr">42</xref>]</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">Antibacterial</td><td align="left" valign="middle" rowspan="1" colspan="1"><italic>D. pulchra</italic> furanones (<bold>25</bold>, <bold>26</bold>)/alga</td><td align="left" valign="middle" rowspan="1" colspan="1">Alkaloid <sup>f</sup></td><td align="left" valign="middle" rowspan="1" colspan="1"><italic>P. aeruginosa</italic> biofilm inhibition</td><td align="left" valign="middle" rowspan="1" colspan="1">1.3 μM <sup>+</sup></td><td align="left" valign="middle" rowspan="1" colspan="1">Undetermined</td><td align="left" valign="middle" rowspan="1" colspan="1">BRA, FRA, USA</td><td align="left" valign="middle" rowspan="1" colspan="1">[<xref rid="B43-marinedrugs-18-00005" ref-type="bibr">43</xref>]</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">Antibacterial</td><td align="left" valign="middle" rowspan="1" colspan="1">aureol B (<bold>27</bold>)/ sponge</td><td align="left" valign="middle" rowspan="1" colspan="1">Terpenoid <sup>e</sup></td><td align="left" valign="middle" rowspan="1" colspan="1">Gram-positive and negative inhibition</td><td align="left" valign="middle" rowspan="1" colspan="1">1 μg/mL <sup>+</sup></td><td align="left" valign="middle" rowspan="1" colspan="1">Undetermined</td><td align="left" valign="middle" rowspan="1" colspan="1">S. KOR</td><td align="left" valign="middle" rowspan="1" colspan="1">[<xref rid="B44-marinedrugs-18-00005" ref-type="bibr">44</xref>]</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">Antibacterial</td><td align="left" valign="middle" rowspan="1" colspan="1">dysidinoid A (<bold>28</bold>)/sponge</td><td align="left" valign="middle" rowspan="1" colspan="1">Terpenoid <sup>e</sup></td><td align="left" valign="middle" rowspan="1" colspan="1">MR <italic>S. aureus</italic> inhibition</td><td align="left" valign="middle" rowspan="1" colspan="1">8 μg/mL **</td><td align="left" valign="middle" rowspan="1" colspan="1">Undetermined</td><td align="left" valign="middle" rowspan="1" colspan="1">CHN</td><td align="left" valign="middle" rowspan="1" colspan="1">[<xref rid="B45-marinedrugs-18-00005" ref-type="bibr">45</xref>]</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">Antibacterial</td><td align="left" valign="middle" rowspan="1" colspan="1"><italic>Eunicea</italic> sp. compounds (<bold>29</bold>, <bold>30</bold>)/sponge</td><td align="left" valign="middle" rowspan="1" colspan="1">Terpenoid <sup>e</sup></td><td align="left" valign="middle" rowspan="1" colspan="1"><italic>P. aeruginosa</italic> and <italic>S. aureus</italic> biofilm inhibition</td><td align="left" valign="middle" rowspan="1" colspan="1">0.5 mg/mL <sup>+</sup></td><td align="left" valign="middle" rowspan="1" colspan="1">Undetermined</td><td align="left" valign="middle" rowspan="1" colspan="1">COL</td><td align="left" valign="middle" rowspan="1" colspan="1">[<xref rid="B46-marinedrugs-18-00005" ref-type="bibr">46</xref>]</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">Antibacterial</td><td align="left" valign="middle" rowspan="1" colspan="1">flavipesin A (<bold>31</bold>)/fungus</td><td align="left" valign="middle" rowspan="1" colspan="1">Polyketide <sup>d</sup></td><td align="left" valign="middle" rowspan="1" colspan="1"><italic>S. aureus</italic> and <italic>B. subtillis</italic> inhibition</td><td align="left" valign="middle" rowspan="1" colspan="1">0.25–8 μg/mL <sup>+</sup></td><td align="left" valign="middle" rowspan="1" colspan="1">Undetermined</td><td align="left" valign="middle" rowspan="1" colspan="1">CHN</td><td align="left" valign="middle" rowspan="1" colspan="1">[<xref rid="B47-marinedrugs-18-00005" ref-type="bibr">47</xref>]</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">Antibacterial</td><td align="left" valign="middle" rowspan="1" colspan="1">gageopeptides A–D (<bold>32–35</bold>)/bacterium</td><td align="left" valign="middle" rowspan="1" colspan="1">Peptide <sup>f</sup></td><td align="left" valign="middle" rowspan="1" colspan="1"><italic>S. aureus</italic> and <italic>B. subtillis</italic> inhibition</td><td align="left" valign="middle" rowspan="1" colspan="1">0.04–0.08 μM <sup>+</sup></td><td align="left" valign="middle" rowspan="1" colspan="1">Undetermined</td><td align="left" valign="middle" rowspan="1" colspan="1">BGD, S. KOR</td><td align="left" valign="middle" rowspan="1" colspan="1">[<xref rid="B48-marinedrugs-18-00005" ref-type="bibr">48</xref>]</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">Antibacterial</td><td align="left" valign="middle" rowspan="1" colspan="1"> gageotetrins A–C (<bold>36–38</bold>)/bacterium</td><td align="left" valign="middle" rowspan="1" colspan="1">Peptide <sup>f</sup></td><td align="left" valign="middle" rowspan="1" colspan="1"><italic>S. aureus</italic> and <italic>B. subtillis</italic> inhibition</td><td align="left" valign="middle" rowspan="1" colspan="1">0.02–0.04 μM <sup>+</sup></td><td align="left" valign="middle" rowspan="1" colspan="1">Undetermined</td><td align="left" valign="middle" rowspan="1" colspan="1">BGD, S. KOR</td><td align="left" valign="middle" rowspan="1" colspan="1">[<xref rid="B49-marinedrugs-18-00005" ref-type="bibr">49</xref>]</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">Antibacterial</td><td align="left" valign="middle" rowspan="1" colspan="1">hormaomycin B (<bold>39</bold>)/bacterium</td><td align="left" valign="middle" rowspan="1" colspan="1">Peptide <sup>f</sup></td><td align="left" valign="middle" rowspan="1" colspan="1"><italic>S. aureus</italic> and <italic>K. rhizophila</italic> inhibition</td><td align="left" valign="middle" rowspan="1" colspan="1">0.4–7 μM <sup>+</sup></td><td align="left" valign="middle" rowspan="1" colspan="1">Undetermined</td><td align="left" valign="middle" rowspan="1" colspan="1">S. KOR</td><td align="left" valign="middle" rowspan="1" colspan="1">[<xref rid="B50-marinedrugs-18-00005" ref-type="bibr">50</xref>]</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">Antibacterial</td><td align="left" valign="middle" rowspan="1" colspan="1">ieodoglucomide C (<bold>40</bold>)/bacterium</td><td align="left" valign="middle" rowspan="1" colspan="1">Glycolipid</td><td align="left" valign="middle" rowspan="1" colspan="1">Gram-positive and negative inhibition</td><td align="left" valign="middle" rowspan="1" colspan="1">0.01–0.05 μM <sup>+</sup></td><td align="left" valign="middle" rowspan="1" colspan="1">Undetermined</td><td align="left" valign="middle" rowspan="1" colspan="1">S. KOR</td><td align="left" valign="middle" rowspan="1" colspan="1">[<xref rid="B51-marinedrugs-18-00005" ref-type="bibr">51</xref>]</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">Antibacterial</td><td align="left" valign="middle" rowspan="1" colspan="1">isoikarugamycin (<bold>41</bold>)/bacterium</td><td align="left" valign="middle" rowspan="1" colspan="1">Alkaloid <sup>f</sup>/ Terpenoid <sup>e</sup></td><td align="left" valign="middle" rowspan="1" colspan="1">MR <italic>S.aureus</italic></td><td align="left" valign="middle" rowspan="1" colspan="1">2–4 μg/mL <sup>+</sup></td><td align="left" valign="middle" rowspan="1" colspan="1">Undetermined</td><td align="left" valign="middle" rowspan="1" colspan="1">ESP</td><td align="left" valign="middle" rowspan="1" colspan="1">[<xref rid="B52-marinedrugs-18-00005" ref-type="bibr">52</xref>]</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">Antibacterial</td><td align="left" valign="middle" rowspan="1" colspan="1">keramadine (<bold>42</bold>)/sponge</td><td align="left" valign="middle" rowspan="1" colspan="1">Alkaloid <sup>f</sup></td><td align="left" valign="middle" rowspan="1" colspan="1"><italic>M. luteus</italic> inhibition</td><td align="left" valign="middle" rowspan="1" colspan="1">4 μg/mL <sup>+</sup></td><td align="left" valign="middle" rowspan="1" colspan="1">Undetermined</td><td align="left" valign="middle" rowspan="1" colspan="1">AUS, JPN </td><td align="left" valign="middle" rowspan="1" colspan="1">[<xref rid="B53-marinedrugs-18-00005" ref-type="bibr">53</xref>]</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">Antibacterial</td><td align="left" valign="middle" rowspan="1" colspan="1"><italic>Ircinia</italic> sp. secosterols (<bold>43</bold>, <bold>44</bold>)/sponge</td><td align="left" valign="middle" rowspan="1" colspan="1">Terpenoid <sup>e</sup></td><td align="left" valign="middle" rowspan="1" colspan="1"><italic>M. luteus</italic> and <italic>S. epidermidis</italic> inhibition</td><td align="left" valign="middle" rowspan="1" colspan="1">3.1, 6.3 μg/mL</td><td align="left" valign="middle" rowspan="1" colspan="1">Undetermined</td><td align="left" valign="middle" rowspan="1" colspan="1">S. KOR</td><td align="left" valign="middle" rowspan="1" colspan="1">[<xref rid="B54-marinedrugs-18-00005" ref-type="bibr">54</xref>,<xref rid="B55-marinedrugs-18-00005" ref-type="bibr">55</xref>]</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">Antibacterial</td><td align="left" valign="middle" rowspan="1" colspan="1"><italic>L. dendyi</italic> terpenoids (<bold>45</bold>, <bold>46</bold>)/sponge</td><td align="left" valign="middle" rowspan="1" colspan="1">Polyketide <sup>d</sup></td><td align="left" valign="middle" rowspan="1" colspan="1">MR <italic>S. aureus</italic> inhibition</td><td align="left" valign="middle" rowspan="1" colspan="1">0.05–0.29 μM</td><td align="left" valign="middle" rowspan="1" colspan="1">Undetermined</td><td align="left" valign="middle" rowspan="1" colspan="1">USA</td><td align="left" valign="middle" rowspan="1" colspan="1">[<xref rid="B56-marinedrugs-18-00005" ref-type="bibr">56</xref>]</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">Antibacterial</td><td align="left" valign="middle" rowspan="1" colspan="1">lindgomycin (<bold>47</bold>)/fungus</td><td align="left" valign="middle" rowspan="1" colspan="1">Polyketide <sup>d</sup></td><td align="left" valign="middle" rowspan="1" colspan="1">MR <italic>S. aureus</italic> inhibition</td><td align="left" valign="middle" rowspan="1" colspan="1">5.1 μM</td><td align="left" valign="middle" rowspan="1" colspan="1">Undetermined</td><td align="left" valign="middle" rowspan="1" colspan="1">CHN, DEU</td><td align="left" valign="middle" rowspan="1" colspan="1">[<xref rid="B57-marinedrugs-18-00005" ref-type="bibr">57</xref>]</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">Antibacterial</td><td align="left" valign="middle" rowspan="1" colspan="1">marformysin D (<bold>48</bold>)/bacterium</td><td align="left" valign="middle" rowspan="1" colspan="1">Peptide <sup>f</sup></td><td align="left" valign="middle" rowspan="1" colspan="1"><italic>M. luteus</italic> inhibition</td><td align="left" valign="middle" rowspan="1" colspan="1">0.063 μg/mL <sup>+</sup></td><td align="left" valign="middle" rowspan="1" colspan="1">Undetermined</td><td align="left" valign="middle" rowspan="1" colspan="1">CHN</td><td align="left" valign="middle" rowspan="1" colspan="1">[<xref rid="B58-marinedrugs-18-00005" ref-type="bibr">58</xref>]</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">Antibacterial</td><td align="left" valign="middle" rowspan="1" colspan="1">mollemycin A (<bold>49</bold>)/bacterium</td><td align="left" valign="middle" rowspan="1" colspan="1">Polyketide <sup>d</sup></td><td align="left" valign="middle" rowspan="1" colspan="1"><italic>S. aureus and S. epidermidis</italic> inhibition</td><td align="left" valign="middle" rowspan="1" colspan="1">0.05 μM</td><td align="left" valign="middle" rowspan="1" colspan="1">Undetermined</td><td align="left" valign="middle" rowspan="1" colspan="1">AUS</td><td align="left" valign="middle" rowspan="1" colspan="1">[<xref rid="B59-marinedrugs-18-00005" ref-type="bibr">59</xref>]</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">Antibacterial</td><td align="left" valign="middle" rowspan="1" colspan="1">neolaurene (<bold>50</bold>)/alga</td><td align="left" valign="middle" rowspan="1" colspan="1">Terpenoid <sup>e</sup></td><td align="left" valign="middle" rowspan="1" colspan="1"><italic>S. typhi</italic> and <italic>S. aureus</italic> inhibition</td><td align="left" valign="middle" rowspan="1" colspan="1">7.5 μg/mL</td><td align="left" valign="middle" rowspan="1" colspan="1">Undetermined</td><td align="left" valign="middle" rowspan="1" colspan="1">MYS</td><td align="left" valign="middle" rowspan="1" colspan="1">[<xref rid="B60-marinedrugs-18-00005" ref-type="bibr">60</xref>]</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">Antibacterial </td><td align="left" valign="middle" rowspan="1" colspan="1">penicyclone A (<bold>51</bold>)/fungus</td><td align="left" valign="middle" rowspan="1" colspan="1">Polyketide <sup>d</sup></td><td align="left" valign="middle" rowspan="1" colspan="1"><italic>S. aureus</italic> inhibition</td><td align="left" valign="middle" rowspan="1" colspan="1">0.3 μg/mL <sup>+</sup></td><td align="left" valign="middle" rowspan="1" colspan="1">Undetermined</td><td align="left" valign="middle" rowspan="1" colspan="1">CHN</td><td align="left" valign="middle" rowspan="1" colspan="1">[<xref rid="B61-marinedrugs-18-00005" ref-type="bibr">61</xref>]</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">Antibacterial</td><td align="left" valign="middle" rowspan="1" colspan="1"><italic>P. oxalicum</italic> enamide (<bold>52</bold>)/fungus</td><td align="left" valign="middle" rowspan="1" colspan="1">Polyketide <sup>d</sup></td><td align="left" valign="middle" rowspan="1" colspan="1"><italic>S. aureus</italic> inhibition</td><td align="left" valign="middle" rowspan="1" colspan="1">2 μg/mL <sup>+</sup></td><td align="left" valign="middle" rowspan="1" colspan="1">Undetermined</td><td align="left" valign="middle" rowspan="1" colspan="1">CHN</td><td align="left" valign="middle" rowspan="1" colspan="1">[<xref rid="B62-marinedrugs-18-00005" ref-type="bibr">62</xref>]</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">Antibacterial</td><td align="left" valign="middle" rowspan="1" colspan="1">puupehenol (<bold>53</bold>)/ sponge</td><td align="left" valign="middle" rowspan="1" colspan="1">Terpenoid <sup>e</sup></td><td align="left" valign="middle" rowspan="1" colspan="1"><italic>B. cereus</italic> and <italic>S. aureus</italic> inhibition</td><td align="left" valign="middle" rowspan="1" colspan="1">10 μg/disk <sup>+</sup></td><td align="left" valign="middle" rowspan="1" colspan="1">Undetermined</td><td align="left" valign="middle" rowspan="1" colspan="1">AUS, USA</td><td align="left" valign="middle" rowspan="1" colspan="1">[<xref rid="B63-marinedrugs-18-00005" ref-type="bibr">63</xref>]</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">Antibacterial</td><td align="left" valign="middle" rowspan="1" colspan="1">phyllospongin E (<bold>54</bold>)/sponge</td><td align="left" valign="middle" rowspan="1" colspan="1">Terpenoid <sup>e</sup></td><td align="left" valign="middle" rowspan="1" colspan="1"><italic>B. cereus</italic> and <italic>S. aureus</italic> inhibition</td><td align="left" valign="middle" rowspan="1" colspan="1">2.5–3.3 μg/mL <sup>+</sup></td><td align="left" valign="middle" rowspan="1" colspan="1">Undetermined</td><td align="left" valign="middle" rowspan="1" colspan="1">EGY, GBR</td><td align="left" valign="middle" rowspan="1" colspan="1">[<xref rid="B64-marinedrugs-18-00005" ref-type="bibr">64</xref>]</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">Antibacterial</td><td align="left" valign="middle" rowspan="1" colspan="1">sarcotrocheliols (<bold>55</bold>, <bold>56</bold>)/soft coral</td><td align="left" valign="middle" rowspan="1" colspan="1">Terpenoid <sup>e</sup></td><td align="left" valign="middle" rowspan="1" colspan="1">MR <italic>S. aureus</italic> inhibition</td><td align="left" valign="middle" rowspan="1" colspan="1">1.5–4.3 μM <sup>+</sup></td><td align="left" valign="middle" rowspan="1" colspan="1">Undetermined</td><td align="left" valign="middle" rowspan="1" colspan="1">SAU</td><td align="left" valign="middle" rowspan="1" colspan="1">[<xref rid="B65-marinedrugs-18-00005" ref-type="bibr">65</xref>]</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">Antibacterial</td><td align="left" valign="middle" rowspan="1" colspan="1">spiromastixone J (<bold>57</bold>)/fungus</td><td align="left" valign="middle" rowspan="1" colspan="1">Polyketide <sup>d</sup></td><td align="left" valign="middle" rowspan="1" colspan="1">MR <italic>S. aureus</italic> inhibition</td><td align="left" valign="middle" rowspan="1" colspan="1">2 μM</td><td align="left" valign="middle" rowspan="1" colspan="1">Undetermined</td><td align="left" valign="middle" rowspan="1" colspan="1">CHN, DEU</td><td align="left" valign="middle" rowspan="1" colspan="1">[<xref rid="B66-marinedrugs-18-00005" ref-type="bibr">66</xref>]</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">Antibacterial</td><td align="left" valign="middle" rowspan="1" colspan="1">stachyin B (<bold>58</bold>)/fungus</td><td align="left" valign="middle" rowspan="1" colspan="1">Alkaloid <sup>f</sup> /Terpenoid <sup>e</sup></td><td align="left" valign="middle" rowspan="1" colspan="1">MR <italic>S. aureus</italic> and <italic>B. subtillis</italic> inhibition</td><td align="left" valign="middle" rowspan="1" colspan="1">1.4–1.7 μM </td><td align="left" valign="middle" rowspan="1" colspan="1">Undetermined</td><td align="left" valign="middle" rowspan="1" colspan="1">CHN, DEU</td><td align="left" valign="middle" rowspan="1" colspan="1">[<xref rid="B67-marinedrugs-18-00005" ref-type="bibr">67</xref>]</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">Antibacterial</td><td align="left" valign="middle" rowspan="1" colspan="1"><italic>Streptomyces</italic> sp. glycoside (<bold>59</bold>)/bacterium</td><td align="left" valign="middle" rowspan="1" colspan="1">Polyketide <sup>d</sup></td><td align="left" valign="middle" rowspan="1" colspan="1"><italic>C. trachomatis</italic> inhibition</td><td align="left" valign="middle" rowspan="1" colspan="1">4.03 μM</td><td align="left" valign="middle" rowspan="1" colspan="1">Undetermined</td><td align="left" valign="middle" rowspan="1" colspan="1">EGY, DEU</td><td align="left" valign="middle" rowspan="1" colspan="1">[<xref rid="B68-marinedrugs-18-00005" ref-type="bibr">68</xref>]</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">Antibacterial</td><td align="left" valign="middle" rowspan="1" colspan="1">subergosterones A–C (<bold>60–62</bold>)/gorgonian coral</td><td align="left" valign="middle" rowspan="1" colspan="1">Terpenoid <sup>e</sup></td><td align="left" valign="middle" rowspan="1" colspan="1"><italic>B. cereus</italic> inhibition</td><td align="left" valign="middle" rowspan="1" colspan="1">1.6–3.1 μM <sup>+</sup></td><td align="left" valign="middle" rowspan="1" colspan="1">Undetermined</td><td align="left" valign="middle" rowspan="1" colspan="1">CHN</td><td align="left" valign="middle" rowspan="1" colspan="1">[<xref rid="B69-marinedrugs-18-00005" ref-type="bibr">69</xref>]</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">Antibacterial</td><td align="left" valign="middle" rowspan="1" colspan="1">vitroprocine A (<bold>63</bold>)/bacterium</td><td align="left" valign="middle" rowspan="1" colspan="1">Polyketide <sup>d</sup></td><td align="left" valign="middle" rowspan="1" colspan="1"><italic>A. baumannii</italic> inhibition</td><td align="left" valign="middle" rowspan="1" colspan="1">8 μg/mL <sup>+</sup></td><td align="left" valign="middle" rowspan="1" colspan="1">Undetermined</td><td align="left" valign="middle" rowspan="1" colspan="1">TWN, USA</td><td align="left" valign="middle" rowspan="1" colspan="1">[<xref rid="B70-marinedrugs-18-00005" ref-type="bibr">70</xref>]</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">Antibacterial</td><td align="left" valign="middle" rowspan="1" colspan="1">xestospongiamide (<bold>64</bold>)/sponge</td><td align="left" valign="middle" rowspan="1" colspan="1">Polyketide <sup>d</sup></td><td align="left" valign="middle" rowspan="1" colspan="1">Gram-positive and negative inhibition</td><td align="left" valign="middle" rowspan="1" colspan="1">2.5 μM <sup>+</sup></td><td align="left" valign="middle" rowspan="1" colspan="1">Undetermined</td><td align="left" valign="middle" rowspan="1" colspan="1">EGY, SAU</td><td align="left" valign="middle" rowspan="1" colspan="1">[<xref rid="B71-marinedrugs-18-00005" ref-type="bibr">71</xref>]</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1"><bold>Antifungal</bold></td><td align="left" valign="middle" rowspan="1" colspan="1">bahamaolide A (<bold>65</bold>)/bacterium</td><td align="left" valign="middle" rowspan="1" colspan="1">Polyketide <sup>d</sup></td><td align="left" valign="middle" rowspan="1" colspan="1"><italic>C. albicans</italic> inhibition</td><td align="left" valign="middle" rowspan="1" colspan="1">1.5–3.1 μg/mL <sup>+</sup></td><td align="left" valign="middle" rowspan="1" colspan="1">ICL inhibition</td><td align="left" valign="middle" rowspan="1" colspan="1">S. KOR</td><td align="left" valign="middle" rowspan="1" colspan="1">[<xref rid="B72-marinedrugs-18-00005" ref-type="bibr">72</xref>]</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">Antifungal</td><td align="left" valign="middle" rowspan="1" colspan="1">heronamide C (<bold>66</bold>)/bacterium</td><td align="left" valign="middle" rowspan="1" colspan="1">Polyketal/<break></break>alkaloid <sup>f</sup></td><td align="left" valign="middle" rowspan="1" colspan="1"><italic>S. pombe</italic> cell inhibition</td><td align="left" valign="middle" rowspan="1" colspan="1">5.8 μM <sup>+</sup></td><td align="left" valign="middle" rowspan="1" colspan="1">Alteration of membrane microdomains</td><td align="left" valign="middle" rowspan="1" colspan="1">JPN</td><td align="left" valign="middle" rowspan="1" colspan="1">[<xref rid="B73-marinedrugs-18-00005" ref-type="bibr">73</xref>]</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">Antifungal</td><td align="left" valign="middle" rowspan="1" colspan="1">forazoline A (<bold>67</bold>)/bacterium</td><td align="left" valign="middle" rowspan="1" colspan="1">Polyketide <sup>d</sup></td><td align="left" valign="middle" rowspan="1" colspan="1"><italic>C. albicans</italic> inhibition</td><td align="left" valign="middle" rowspan="1" colspan="1">16 μg/mL <sup>+</sup></td><td align="left" valign="middle" rowspan="1" colspan="1">Affected membrane integrity</td><td align="left" valign="middle" rowspan="1" colspan="1">USA</td><td align="left" valign="middle" rowspan="1" colspan="1">[<xref rid="B74-marinedrugs-18-00005" ref-type="bibr">74</xref>]</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">Antifungal</td><td align="left" valign="middle" rowspan="1" colspan="1">aaptamine derivative (<bold>68</bold>)/sponge</td><td align="left" valign="middle" rowspan="1" colspan="1">Alkaloid <sup>f</sup></td><td align="left" valign="middle" rowspan="1" colspan="1"><italic>T. rubrum</italic> inhibition</td><td align="left" valign="middle" rowspan="1" colspan="1">4 μg/mL <sup>+</sup></td><td align="left" valign="middle" rowspan="1" colspan="1">Undetermined</td><td align="left" valign="middle" rowspan="1" colspan="1">CHN</td><td align="left" valign="middle" rowspan="1" colspan="1">[<xref rid="B75-marinedrugs-18-00005" ref-type="bibr">75</xref>]</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">Antifungal</td><td align="left" valign="middle" rowspan="1" colspan="1">amphidinin G (<bold>69</bold>)/dinoflagellate</td><td align="left" valign="middle" rowspan="1" colspan="1">Polyketide <sup>d</sup></td><td align="left" valign="middle" rowspan="1" colspan="1"><italic>T. mentagrophytes</italic> inhibition</td><td align="left" valign="middle" rowspan="1" colspan="1">8 μg/mL</td><td align="left" valign="middle" rowspan="1" colspan="1">Undetermined</td><td align="left" valign="middle" rowspan="1" colspan="1">JPN</td><td align="left" valign="middle" rowspan="1" colspan="1">[<xref rid="B76-marinedrugs-18-00005" ref-type="bibr">76</xref>]</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">Antifungal</td><td align="left" valign="middle" rowspan="1" colspan="1">amphidinol 18 (<bold>70</bold>)/dinoflagellate</td><td align="left" valign="middle" rowspan="1" colspan="1">Polyketide <sup>d</sup></td><td align="left" valign="middle" rowspan="1" colspan="1"><italic>C. albicans</italic> inhibition</td><td align="left" valign="middle" rowspan="1" colspan="1">9 μg/mL <sup>+</sup></td><td align="left" valign="middle" rowspan="1" colspan="1">Undetermined</td><td align="left" valign="middle" rowspan="1" colspan="1">ITA</td><td align="left" valign="middle" rowspan="1" colspan="1">[<xref rid="B77-marinedrugs-18-00005" ref-type="bibr">77</xref>]</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">Antifungal</td><td align="left" valign="middle" rowspan="1" colspan="1">crambescin homologues (<bold>71–73</bold>)/sponge</td><td align="left" valign="middle" rowspan="1" colspan="1">Alkaloid <sup>f</sup></td><td align="left" valign="middle" rowspan="1" colspan="1"><italic>C. neoformans</italic> var. <italic>gattii</italic> inhibition</td><td align="left" valign="middle" rowspan="1" colspan="1">0.85–2.6 μM <sup>+</sup></td><td align="left" valign="middle" rowspan="1" colspan="1">Undetermined</td><td align="left" valign="middle" rowspan="1" colspan="1">USA</td><td align="left" valign="middle" rowspan="1" colspan="1">[<xref rid="B78-marinedrugs-18-00005" ref-type="bibr">78</xref>]</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">Antifungal</td><td align="left" valign="middle" rowspan="1" colspan="1">coustesides C and D (<bold>74</bold>, <bold>75</bold>)/sea cucumber</td><td align="left" valign="middle" rowspan="1" colspan="1">Terpenoid glycoside <sup>e</sup></td><td align="left" valign="middle" rowspan="1" colspan="1"><italic>C. albicans</italic> inhibition</td><td align="left" valign="middle" rowspan="1" colspan="1">1 mg/mL <sup>++</sup></td><td align="left" valign="middle" rowspan="1" colspan="1">Undetermined</td><td align="left" valign="middle" rowspan="1" colspan="1">EGY, S.KOR</td><td align="left" valign="middle" rowspan="1" colspan="1">[<xref rid="B79-marinedrugs-18-00005" ref-type="bibr">79</xref>]</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">Antifungal</td><td align="left" valign="middle" rowspan="1" colspan="1"><italic>L. okamurai</italic> laurenes (<bold>76–78</bold>)/alga</td><td align="left" valign="middle" rowspan="1" colspan="1">Terpenoid <sup>e</sup></td><td align="left" valign="middle" rowspan="1" colspan="1"><italic>C. glabrata</italic> inhibition</td><td align="left" valign="middle" rowspan="1" colspan="1">2–4 μg/mL **</td><td align="left" valign="middle" rowspan="1" colspan="1">Undetermined</td><td align="left" valign="middle" rowspan="1" colspan="1">CHN</td><td align="left" valign="middle" rowspan="1" colspan="1">[<xref rid="B80-marinedrugs-18-00005" ref-type="bibr">80</xref>,<xref rid="B81-marinedrugs-18-00005" ref-type="bibr">81</xref>]</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">Antifungal</td><td align="left" valign="middle" rowspan="1" colspan="1">mohangamide A (<bold>79</bold>)/bacterium</td><td align="left" valign="middle" rowspan="1" colspan="1">Peptide <sup>f</sup></td><td align="left" valign="middle" rowspan="1" colspan="1"><italic>C. albicans</italic> isocitrate lyase inhibition</td><td align="left" valign="middle" rowspan="1" colspan="1">4.4 μM</td><td align="left" valign="middle" rowspan="1" colspan="1">Undetermined</td><td align="left" valign="middle" rowspan="1" colspan="1">S. KOR</td><td align="left" valign="middle" rowspan="1" colspan="1">[<xref rid="B82-marinedrugs-18-00005" ref-type="bibr">82</xref>]</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">Antifungal</td><td align="left" valign="middle" rowspan="1" colspan="1">pleosporallin E (<bold>80</bold>)/fungus</td><td align="left" valign="middle" rowspan="1" colspan="1">Polyketide <sup>d</sup></td><td align="left" valign="middle" rowspan="1" colspan="1"><italic>C. albicans</italic> inhibition</td><td align="left" valign="middle" rowspan="1" colspan="1">7.44 μg/mL <sup>+</sup></td><td align="left" valign="middle" rowspan="1" colspan="1">Undetermined</td><td align="left" valign="middle" rowspan="1" colspan="1">CHN</td><td align="left" valign="middle" rowspan="1" colspan="1">[<xref rid="B83-marinedrugs-18-00005" ref-type="bibr">83</xref>]</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">Antifungal</td><td align="left" valign="middle" rowspan="1" colspan="1"><italic>S. purpurea</italic> lysophospholipid (<bold>81</bold>)/sponge</td><td align="left" valign="middle" rowspan="1" colspan="1">Phospholipid</td><td align="left" valign="middle" rowspan="1" colspan="1"><italic>C. glabrata</italic> and <italic>C. neoformans</italic> inhibition</td><td align="left" valign="middle" rowspan="1" colspan="1">4 μg/mL <sup>+</sup></td><td align="left" valign="middle" rowspan="1" colspan="1">Undetermined</td><td align="left" valign="middle" rowspan="1" colspan="1">CHN</td><td align="left" valign="middle" rowspan="1" colspan="1">[<xref rid="B84-marinedrugs-18-00005" ref-type="bibr">84</xref>]</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">Antifungal</td><td align="left" valign="middle" rowspan="1" colspan="1">taurospongin A (<bold>82</bold>)/sponge</td><td align="left" valign="middle" rowspan="1" colspan="1">Polyketide <sup>d</sup></td><td align="left" valign="middle" rowspan="1" colspan="1"><italic>C. neoformans</italic> inhibition</td><td align="left" valign="middle" rowspan="1" colspan="1">1 μg/mL <sup>+</sup></td><td align="left" valign="middle" rowspan="1" colspan="1">Undetermined</td><td align="left" valign="middle" rowspan="1" colspan="1">AUS, JPN</td><td align="left" valign="middle" rowspan="1" colspan="1">[<xref rid="B85-marinedrugs-18-00005" ref-type="bibr">85</xref>]</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">Antifungal</td><td align="left" valign="middle" rowspan="1" colspan="1">variegatuside D (<bold>83</bold>)/sea cucumber</td><td align="left" valign="middle" rowspan="1" colspan="1">Terpenoid glycoside <sup>e</sup></td><td align="left" valign="middle" rowspan="1" colspan="1">Several <italic>Candida</italic> species inhibition</td><td align="left" valign="middle" rowspan="1" colspan="1">3.4–13.6 μg/mL <sup>+</sup></td><td align="left" valign="middle" rowspan="1" colspan="1">Undetermined</td><td align="left" valign="middle" rowspan="1" colspan="1">CHN</td><td align="left" valign="middle" rowspan="1" colspan="1">[<xref rid="B86-marinedrugs-18-00005" ref-type="bibr">86</xref>]</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">Antifungal</td><td align="left" valign="middle" rowspan="1" colspan="1">xestospongiamide (<bold>64</bold>)/sponge</td><td align="left" valign="middle" rowspan="1" colspan="1">Polyketide <sup>d</sup></td><td align="left" valign="middle" rowspan="1" colspan="1"><italic>A. niger</italic> and <italic>C. albicans</italic> inhibition</td><td align="left" valign="middle" rowspan="1" colspan="1">>5 μM <sup>+</sup></td><td align="left" valign="middle" rowspan="1" colspan="1">Undetermined</td><td align="left" valign="middle" rowspan="1" colspan="1">EGY, SAU</td><td align="left" valign="middle" rowspan="1" colspan="1">[<xref rid="B71-marinedrugs-18-00005" ref-type="bibr">71</xref>]</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1"><bold>Antimalarial</bold></td><td align="left" valign="middle" rowspan="1" colspan="1"><italic>C. hooperi</italic> isonitrile (<bold>84</bold>)/sponge</td><td align="left" valign="middle" rowspan="1" colspan="1">Terpenoid <sup>e</sup></td><td align="left" valign="middle" rowspan="1" colspan="1"><italic>P. falciparum</italic> D6 and W2 strain inhibition</td><td align="left" valign="middle" rowspan="1" colspan="1">4.3–4.7 nM</td><td align="left" valign="middle" rowspan="1" colspan="1">β-hematin inhibition</td><td align="left" valign="middle" rowspan="1" colspan="1">USA, ZAF</td><td align="left" valign="middle" rowspan="1" colspan="1">[<xref rid="B87-marinedrugs-18-00005" ref-type="bibr">87</xref>]</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">Antimalarial</td><td align="left" valign="middle" rowspan="1" colspan="1">actinoramide A (<bold>85</bold>)/bacterium</td><td align="left" valign="middle" rowspan="1" colspan="1">Peptide <sup>f</sup></td><td align="left" valign="middle" rowspan="1" colspan="1"><italic>P. falciparum</italic> strains inhibition</td><td align="left" valign="middle" rowspan="1" colspan="1">0.2 μM</td><td align="left" valign="middle" rowspan="1" colspan="1">Undetermined</td><td align="left" valign="middle" rowspan="1" colspan="1">CRI, USA</td><td align="left" valign="middle" rowspan="1" colspan="1">[<xref rid="B88-marinedrugs-18-00005" ref-type="bibr">88</xref>]</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">Antimalarial</td><td align="left" valign="middle" rowspan="1" colspan="1">diacarperoxide J (<bold>86</bold>)/sponge</td><td align="left" valign="middle" rowspan="1" colspan="1">Terpenoid <sup>e</sup></td><td align="left" valign="middle" rowspan="1" colspan="1"><italic>P. falciparum</italic> D6 and W2 strain inhibition</td><td align="left" valign="middle" rowspan="1" colspan="1">1.6–1.8 μM</td><td align="left" valign="middle" rowspan="1" colspan="1">Undetermined</td><td align="left" valign="middle" rowspan="1" colspan="1">CHN, USA</td><td align="left" valign="middle" rowspan="1" colspan="1">[<xref rid="B89-marinedrugs-18-00005" ref-type="bibr">89</xref>]</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">Antimalarial</td><td align="left" valign="middle" rowspan="1" colspan="1">laevigatol A (<bold>87</bold>)/soft coral</td><td align="left" valign="middle" rowspan="1" colspan="1">Terpenoid <sup>e</sup></td><td align="left" valign="middle" rowspan="1" colspan="1"><italic>P. falciparum</italic> NF54 strain inhibition</td><td align="left" valign="middle" rowspan="1" colspan="1">3.0 μM</td><td align="left" valign="middle" rowspan="1" colspan="1">Undetermined</td><td align="left" valign="middle" rowspan="1" colspan="1">CHE, DEU, S. KOR, VNM</td><td align="left" valign="middle" rowspan="1" colspan="1">[<xref rid="B90-marinedrugs-18-00005" ref-type="bibr">90</xref>]</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">Antimalarial </td><td align="left" valign="middle" rowspan="1" colspan="1">mollemycin A (<bold>49</bold>)/bacterium</td><td align="left" valign="middle" rowspan="1" colspan="1">Polyketide <sup>d</sup></td><td align="left" valign="middle" rowspan="1" colspan="1"><italic>P. falciparum</italic> 3D7and Dd2 strain inhibition</td><td align="left" valign="middle" rowspan="1" colspan="1">7–9 nM</td><td align="left" valign="middle" rowspan="1" colspan="1">Undetermined</td><td align="left" valign="middle" rowspan="1" colspan="1">AUS</td><td align="left" valign="middle" rowspan="1" colspan="1">[<xref rid="B59-marinedrugs-18-00005" ref-type="bibr">59</xref>]</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">Antimalarial</td><td align="left" valign="middle" rowspan="1" colspan="1">mon amphilectines B and C (<bold>88</bold>, <bold>89</bold>)/sponge</td><td align="left" valign="middle" rowspan="1" colspan="1">Terpenoid <sup>e</sup></td><td align="left" valign="middle" rowspan="1" colspan="1"><italic>P. falciparum</italic> 3D7strain inhibition</td><td align="left" valign="middle" rowspan="1" colspan="1">44 nM</td><td align="left" valign="middle" rowspan="1" colspan="1">Undetermined</td><td align="left" valign="middle" rowspan="1" colspan="1">USA</td><td align="left" valign="middle" rowspan="1" colspan="1">[<xref rid="B91-marinedrugs-18-00005" ref-type="bibr">91</xref>]</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">Antimalarial</td><td align="left" valign="middle" rowspan="1" colspan="1">netamine K (<bold>90</bold>)/sponge</td><td align="left" valign="middle" rowspan="1" colspan="1">Alkaloid <sup>f</sup></td><td align="left" valign="middle" rowspan="1" colspan="1"><italic>P. falciparum</italic> inhibition</td><td align="left" valign="middle" rowspan="1" colspan="1">2.4 μM</td><td align="left" valign="middle" rowspan="1" colspan="1">Undetermined</td><td align="left" valign="middle" rowspan="1" colspan="1">BEL, FRA, ISR</td><td align="left" valign="middle" rowspan="1" colspan="1">[<xref rid="B92-marinedrugs-18-00005" ref-type="bibr">92</xref>]</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">Antimalarial</td><td align="left" valign="middle" rowspan="1" colspan="1"><italic>P. ocellata</italic> sesquiterpenes (<bold>91–93</bold>)/nudibranch</td><td align="left" valign="middle" rowspan="1" colspan="1">Terpenoid <sup>e</sup></td><td align="left" valign="middle" rowspan="1" colspan="1"><italic>P. falciparum</italic> inhibition</td><td align="left" valign="middle" rowspan="1" colspan="1">0.26–0.3 μM</td><td align="left" valign="middle" rowspan="1" colspan="1">Undetermined</td><td align="left" valign="middle" rowspan="1" colspan="1">AUS, ITA</td><td align="left" valign="middle" rowspan="1" colspan="1">[<xref rid="B93-marinedrugs-18-00005" ref-type="bibr">93</xref>]</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">Antimalarial</td><td align="left" valign="middle" rowspan="1" colspan="1"><italic>P. simplex</italic> polyketide (<bold>94</bold>)/sponge</td><td align="left" valign="middle" rowspan="1" colspan="1">Polyketide <sup>d</sup></td><td align="left" valign="middle" rowspan="1" colspan="1"><italic>P. falciparum</italic> D10 and W2 strain inhibition</td><td align="left" valign="middle" rowspan="1" colspan="1">2.7–4.0 μM</td><td align="left" valign="middle" rowspan="1" colspan="1">Undetermined</td><td align="left" valign="middle" rowspan="1" colspan="1">CHN, ITA</td><td align="left" valign="middle" rowspan="1" colspan="1">[<xref rid="B94-marinedrugs-18-00005" ref-type="bibr">94</xref>]</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1"><bold>Antiprotozoal</bold></td><td align="left" valign="middle" rowspan="1" colspan="1">plakortide E (<bold>95</bold>)/sponge</td><td align="left" valign="middle" rowspan="1" colspan="1">Polyketide <sup>d</sup></td><td align="left" valign="middle" rowspan="1" colspan="1"><italic>T. brucei</italic> inhibition</td><td align="left" valign="middle" rowspan="1" colspan="1">5 μM</td><td align="left" valign="middle" rowspan="1" colspan="1">Rhodesain inhibition</td><td align="left" valign="middle" rowspan="1" colspan="1">EGY, DEU</td><td align="left" valign="middle" rowspan="1" colspan="1">[<xref rid="B95-marinedrugs-18-00005" ref-type="bibr">95</xref>]</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">Antiprotozoal</td><td align="left" valign="middle" rowspan="1" colspan="1">batzelladine L (<bold>96</bold>)/sponge</td><td align="left" valign="middle" rowspan="1" colspan="1">Alkaloid <sup>f</sup></td><td align="left" valign="middle" rowspan="1" colspan="1"><italic>T. cruzi</italic> and <italic>L. infantum</italic> inhibition</td><td align="left" valign="middle" rowspan="1" colspan="1">2 μM</td><td align="left" valign="middle" rowspan="1" colspan="1">Enhanced ROS generation</td><td align="left" valign="middle" rowspan="1" colspan="1">BRA, CAN</td><td align="left" valign="middle" rowspan="1" colspan="1">[<xref rid="B96-marinedrugs-18-00005" ref-type="bibr">96</xref>]</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">Antiprotozoal</td><td align="left" valign="middle" rowspan="1" colspan="1">actinoporin A (<bold>97</bold>)/ bacterium</td><td align="left" valign="middle" rowspan="1" colspan="1">Polyketide <sup>d</sup></td><td align="left" valign="middle" rowspan="1" colspan="1"><italic>T. b. brucei</italic> inhibition</td><td align="left" valign="middle" rowspan="1" colspan="1">15 μM</td><td align="left" valign="middle" rowspan="1" colspan="1">Undetermined</td><td align="left" valign="middle" rowspan="1" colspan="1">AUS, DEU, EGY, GBR</td><td align="left" valign="middle" rowspan="1" colspan="1">[<xref rid="B97-marinedrugs-18-00005" ref-type="bibr">97</xref>]</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">Antiprotozoal</td><td align="left" valign="middle" rowspan="1" colspan="1">astropectenol A (<bold>98</bold>)/soft coral</td><td align="left" valign="middle" rowspan="1" colspan="1">Terpenoid <sup>e</sup></td><td align="left" valign="middle" rowspan="1" colspan="1"><italic>T. brucei</italic> inhibition</td><td align="left" valign="middle" rowspan="1" colspan="1">1.6 μM</td><td align="left" valign="middle" rowspan="1" colspan="1">Undetermined</td><td align="left" valign="middle" rowspan="1" colspan="1">DEU, VNM, S. KOR</td><td align="left" valign="middle" rowspan="1" colspan="1">[<xref rid="B98-marinedrugs-18-00005" ref-type="bibr">98</xref>]</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">Antiprotozoal</td><td align="left" valign="middle" rowspan="1" colspan="1"><italic>H. simulans</italic> sterol (<bold>99</bold>) sponge</td><td align="left" valign="middle" rowspan="1" colspan="1">Terpenoid <sup>e</sup></td><td align="left" valign="middle" rowspan="1" colspan="1"><italic>T. b. brucei</italic> inhibition</td><td align="left" valign="middle" rowspan="1" colspan="1">4.6 μM <sup>+</sup></td><td align="left" valign="middle" rowspan="1" colspan="1">Undetermined</td><td align="left" valign="middle" rowspan="1" colspan="1">IRL, GBR</td><td align="left" valign="middle" rowspan="1" colspan="1">[<xref rid="B99-marinedrugs-18-00005" ref-type="bibr">99</xref>]</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">Antiprotozoal</td><td align="left" valign="middle" rowspan="1" colspan="1">lobosamide A (<bold>100</bold>)/bacterium</td><td align="left" valign="middle" rowspan="1" colspan="1">Alkaloid <sup>f</sup></td><td align="left" valign="middle" rowspan="1" colspan="1"><italic>T. b. brucei</italic> inhibition</td><td align="left" valign="middle" rowspan="1" colspan="1">0.8 μM</td><td align="left" valign="middle" rowspan="1" colspan="1">Undetermined</td><td align="left" valign="middle" rowspan="1" colspan="1">USA</td><td align="left" valign="middle" rowspan="1" colspan="1">[<xref rid="B100-marinedrugs-18-00005" ref-type="bibr">100</xref>]</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">Antiprotozoal</td><td align="left" valign="middle" rowspan="1" colspan="1">lobocrasols A and C (<bold>101</bold>, <bold>102</bold>)/soft corals</td><td align="left" valign="middle" rowspan="1" colspan="1">Terpenoid <sup>e</sup></td><td align="left" valign="middle" rowspan="1" colspan="1"><italic>L. donovani</italic> inhibition</td><td align="left" valign="middle" rowspan="1" colspan="1">0.18 μM</td><td align="left" valign="middle" rowspan="1" colspan="1">Undetermined</td><td align="left" valign="middle" rowspan="1" colspan="1">CHE, DEU, S. KOR, VNM</td><td align="left" valign="middle" rowspan="1" colspan="1">[<xref rid="B90-marinedrugs-18-00005" ref-type="bibr">90</xref>]</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">Antiprotozoal</td><td align="left" valign="middle" rowspan="1" colspan="1">mangromicin A (<bold>103</bold>)/fungus</td><td align="left" valign="middle" rowspan="1" colspan="1">Polyketide <sup>d</sup></td><td align="left" valign="middle" rowspan="1" colspan="1"><italic>T. b. brucei</italic> inhibition</td><td align="left" valign="middle" rowspan="1" colspan="1">2.44 µg/mL</td><td align="left" valign="middle" rowspan="1" colspan="1">Undetermined</td><td align="left" valign="middle" rowspan="1" colspan="1">JPN</td><td align="left" valign="middle" rowspan="1" colspan="1">[<xref rid="B101-marinedrugs-18-00005" ref-type="bibr">101</xref>]</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">Antiprotozoal</td><td align="left" valign="middle" rowspan="1" colspan="1">crassumols D and E (<bold>104</bold>, <bold>105</bold>)/soft corals</td><td align="left" valign="middle" rowspan="1" colspan="1">Terpenoid <sup>e</sup></td><td align="left" valign="middle" rowspan="1" colspan="1"><italic>T. b. rhodesiense</italic> inhibition</td><td align="left" valign="middle" rowspan="1" colspan="1">0.61 and 0.72 μM</td><td align="left" valign="middle" rowspan="1" colspan="1">Undetermined</td><td align="left" valign="middle" rowspan="1" colspan="1">CHE, DEU, S. KOR, VNM</td><td align="left" valign="middle" rowspan="1" colspan="1">[<xref rid="B90-marinedrugs-18-00005" ref-type="bibr">90</xref>]</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">Antiprotozoal</td><td align="left" valign="middle" rowspan="1" colspan="1">sesterstamide (<bold>106</bold>)/sponge </td><td align="left" valign="middle" rowspan="1" colspan="1">Terpenoid <sup>e</sup></td><td align="left" valign="middle" rowspan="1" colspan="1"><italic>L. donovani</italic> inhibition</td><td align="left" valign="middle" rowspan="1" colspan="1">32.9 µg/mL</td><td align="left" valign="middle" rowspan="1" colspan="1">Undetermined</td><td align="left" valign="middle" rowspan="1" colspan="1">CHN</td><td align="left" valign="middle" rowspan="1" colspan="1">[<xref rid="B102-marinedrugs-18-00005" ref-type="bibr">102</xref>]</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">Antiprotozoal</td><td align="left" valign="middle" rowspan="1" colspan="1">shagene A (<bold>107</bold>)/soft coral</td><td align="left" valign="middle" rowspan="1" colspan="1">Terpenoid <sup>e</sup></td><td align="left" valign="middle" rowspan="1" colspan="1"><italic>L. donovani</italic> inhibition</td><td align="left" valign="middle" rowspan="1" colspan="1">5 μM</td><td align="left" valign="middle" rowspan="1" colspan="1">Undetermined</td><td align="left" valign="middle" rowspan="1" colspan="1">AUS, USA</td><td align="left" valign="middle" rowspan="1" colspan="1">[<xref rid="B103-marinedrugs-18-00005" ref-type="bibr">103</xref>]</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1"><bold>Antituberculosis</bold></td><td align="left" valign="middle" rowspan="1" colspan="1">aaptamine analog (<bold>108</bold>)/sponge</td><td align="left" valign="middle" rowspan="1" colspan="1">Alkaloid <sup>f</sup></td><td align="left" valign="middle" rowspan="1" colspan="1"><italic>M. smegmatis</italic> inhibition</td><td align="left" valign="middle" rowspan="1" colspan="1">6.25 μg/mL <sup>+</sup></td><td align="left" valign="middle" rowspan="1" colspan="1">Undetermined</td><td align="left" valign="middle" rowspan="1" colspan="1">JPN</td><td align="left" valign="middle" rowspan="1" colspan="1">[<xref rid="B104-marinedrugs-18-00005" ref-type="bibr">104</xref>]</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">Antituberculosis</td><td align="left" valign="middle" rowspan="1" colspan="1">callyaerins A and B (<bold>109</bold>, <bold>110</bold>)/sponge</td><td align="left" valign="middle" rowspan="1" colspan="1">Peptide <sup>f</sup></td><td align="left" valign="middle" rowspan="1" colspan="1"><italic>M. tuberculosis</italic> inhibition</td><td align="left" valign="middle" rowspan="1" colspan="1">2, 5 μM **</td><td align="left" valign="middle" rowspan="1" colspan="1">Undetermined</td><td align="left" valign="middle" rowspan="1" colspan="1">CHN, DEU, NLD</td><td align="left" valign="middle" rowspan="1" colspan="1">[<xref rid="B105-marinedrugs-18-00005" ref-type="bibr">105</xref>]</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">Antituberculosis</td><td align="left" valign="middle" rowspan="1" colspan="1">denigrin C (<bold>111</bold>)/sponge</td><td align="left" valign="middle" rowspan="1" colspan="1">Alkaloid <sup>f</sup></td><td align="left" valign="middle" rowspan="1" colspan="1"><italic>M. tuberculosis</italic> H<sub>37</sub>Rv inhibition</td><td align="left" valign="middle" rowspan="1" colspan="1">4 μg/mL <sup>+</sup></td><td align="left" valign="middle" rowspan="1" colspan="1">Undetermined</td><td align="left" valign="middle" rowspan="1" colspan="1">IND</td><td align="left" valign="middle" rowspan="1" colspan="1">[<xref rid="B106-marinedrugs-18-00005" ref-type="bibr">106</xref>]</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">Antituberculosis</td><td align="left" valign="middle" rowspan="1" colspan="1">oxazinin A (<bold>112</bold>)/fungus</td><td align="left" valign="middle" rowspan="1" colspan="1">Polyketide <sup>d</sup></td><td align="left" valign="middle" rowspan="1" colspan="1"><italic>M. tuberculosis</italic> inhibition</td><td align="left" valign="middle" rowspan="1" colspan="1">2.9 μM</td><td align="left" valign="middle" rowspan="1" colspan="1">Undetermined</td><td align="left" valign="middle" rowspan="1" colspan="1">USA</td><td align="left" valign="middle" rowspan="1" colspan="1">[<xref rid="B107-marinedrugs-18-00005" ref-type="bibr">107</xref>]</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1"><bold>Antiviral</bold></td><td align="left" valign="middle" rowspan="1" colspan="1">pateamine A (<bold>113</bold>)/sponge</td><td align="left" valign="middle" rowspan="1" colspan="1">Mixed Biogenesis</td><td align="left" valign="middle" rowspan="1" colspan="1">Sindbis virus mRNA translation inhibition</td><td align="left" valign="middle" rowspan="1" colspan="1">>100 nM</td><td align="left" valign="middle" rowspan="1" colspan="1">nsP1 or nsP2 viral protein synthesis inhibition </td><td align="left" valign="middle" rowspan="1" colspan="1">CAN, ESP, NZL </td><td align="left" valign="middle" rowspan="1" colspan="1">[<xref rid="B108-marinedrugs-18-00005" ref-type="bibr">108</xref>]</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">Antiviral</td><td align="left" valign="middle" rowspan="1" colspan="1">abyssomicin 2 (<bold>114</bold>)/bacterium</td><td align="left" valign="middle" rowspan="1" colspan="1">Polyketide <sup>d</sup></td><td align="left" valign="middle" rowspan="1" colspan="1">HIV-1 reactivation</td><td align="left" valign="middle" rowspan="1" colspan="1">13.9 μM</td><td align="left" valign="middle" rowspan="1" colspan="1">Increased viral RNA in CD4<sup>+</sup> T cells</td><td align="left" valign="middle" rowspan="1" colspan="1">USA</td><td align="left" valign="middle" rowspan="1" colspan="1">[<xref rid="B109-marinedrugs-18-00005" ref-type="bibr">109</xref>]</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">Antiviral</td><td align="left" valign="middle" rowspan="1" colspan="1">8,4′’’-dieckol (<bold>115</bold>)/alga</td><td align="left" valign="middle" rowspan="1" colspan="1">Polyketide <sup>d</sup></td><td align="left" valign="middle" rowspan="1" colspan="1">HIV-1 inhibition</td><td align="left" valign="middle" rowspan="1" colspan="1">10 μM * </td><td align="left" valign="middle" rowspan="1" colspan="1">Reverse transcriptase inhibition</td><td align="left" valign="middle" rowspan="1" colspan="1">S. KOR</td><td align="left" valign="middle" rowspan="1" colspan="1">[<xref rid="B110-marinedrugs-18-00005" ref-type="bibr">110</xref>]</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">Antiviral</td><td align="left" valign="middle" rowspan="1" colspan="1">truncateol M (<bold>116</bold>)/fungus</td><td align="left" valign="middle" rowspan="1" colspan="1">Terpenoid <sup>e</sup></td><td align="left" valign="middle" rowspan="1" colspan="1">H1N1 influenza A virus inhibition</td><td align="left" valign="middle" rowspan="1" colspan="1">8.8 μM</td><td align="left" valign="middle" rowspan="1" colspan="1">Virion assembly/release inhibition</td><td align="left" valign="middle" rowspan="1" colspan="1">CHN, DEU</td><td align="left" valign="middle" rowspan="1" colspan="1">[<xref rid="B111-marinedrugs-18-00005" ref-type="bibr">111</xref>]</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">Antiviral</td><td align="left" valign="middle" rowspan="1" colspan="1">neoechinulin B (<bold>117</bold>)/fungus</td><td align="left" valign="middle" rowspan="1" colspan="1">Alkaloid <sup>f</sup></td><td align="left" valign="middle" rowspan="1" colspan="1">H3N2, H1N1 A influenza virus inhibition</td><td align="left" valign="middle" rowspan="1" colspan="1">17-22 μM</td><td align="left" valign="middle" rowspan="1" colspan="1">Hemagglutinin inhibition</td><td align="left" valign="middle" rowspan="1" colspan="1">CHN, DEU</td><td align="left" valign="middle" rowspan="1" colspan="1">[<xref rid="B112-marinedrugs-18-00005" ref-type="bibr">112</xref>] </td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">Antiviral</td><td align="left" valign="middle" rowspan="1" colspan="1">thaixylomolin I (<bold>118</bold>)/mangrove</td><td align="left" valign="middle" rowspan="1" colspan="1">Terpenoid <sup>e</sup></td><td align="left" valign="middle" rowspan="1" colspan="1">H1N1 influenza A virus inhibition</td><td align="left" valign="middle" rowspan="1" colspan="1">77 μM</td><td align="left" valign="middle" rowspan="1" colspan="1">Undetermined</td><td align="left" valign="middle" rowspan="1" colspan="1">CHN, DEU, THAI</td><td align="left" valign="middle" rowspan="1" colspan="1">[<xref rid="B113-marinedrugs-18-00005" ref-type="bibr">113</xref>]</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">Antiviral</td><td align="left" valign="middle" rowspan="1" colspan="1">aaptamine derivative (<bold>68</bold>)/sponge</td><td align="left" valign="middle" rowspan="1" colspan="1">Alkaloid <sup>f</sup></td><td align="left" valign="middle" rowspan="1" colspan="1">HIV-1 inhibition</td><td align="left" valign="middle" rowspan="1" colspan="1">10 μM *</td><td align="left" valign="middle" rowspan="1" colspan="1">Undetermined</td><td align="left" valign="middle" rowspan="1" colspan="1">CHN</td><td align="left" valign="middle" rowspan="1" colspan="1">[<xref rid="B75-marinedrugs-18-00005" ref-type="bibr">75</xref>]</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">Antiviral </td><td align="left" valign="middle" rowspan="1" colspan="1">aflaquinolone B derivative (<bold>119</bold>)/fungus</td><td align="left" valign="middle" rowspan="1" colspan="1">Mixed biogenesis</td><td align="left" valign="middle" rowspan="1" colspan="1">RSV inhibition</td><td align="left" valign="middle" rowspan="1" colspan="1">0.042 μM</td><td align="left" valign="middle" rowspan="1" colspan="1">Undetermined</td><td align="left" valign="middle" rowspan="1" colspan="1">CHN</td><td align="left" valign="middle" rowspan="1" colspan="1">[<xref rid="B114-marinedrugs-18-00005" ref-type="bibr">114</xref>]</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">Antiviral</td><td align="left" valign="middle" rowspan="1" colspan="1"><italic>A. terreus</italic> lactones (<bold>120</bold>, <bold>121</bold>)/fungus</td><td align="left" valign="middle" rowspan="1" colspan="1">Polyketide <sup>d</sup></td><td align="left" valign="middle" rowspan="1" colspan="1">HSV-1 inhibition</td><td align="left" valign="middle" rowspan="1" colspan="1">6.34 μg/mL</td><td align="left" valign="middle" rowspan="1" colspan="1">Undetermined</td><td align="left" valign="middle" rowspan="1" colspan="1">CHN</td><td align="left" valign="middle" rowspan="1" colspan="1">[<xref rid="B115-marinedrugs-18-00005" ref-type="bibr">115</xref>]</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">Antiviral</td><td align="left" valign="middle" rowspan="1" colspan="1">chartarutine B (<bold>122</bold>)/fungus</td><td align="left" valign="middle" rowspan="1" colspan="1">Alkaloid <sup>f</sup>/terpenoid <sup>e</sup></td><td align="left" valign="middle" rowspan="1" colspan="1">HIV-1 inhibition</td><td align="left" valign="middle" rowspan="1" colspan="1">4.9 μM</td><td align="left" valign="middle" rowspan="1" colspan="1">Undetermined</td><td align="left" valign="middle" rowspan="1" colspan="1">CHN, DEU</td><td align="left" valign="middle" rowspan="1" colspan="1">[<xref rid="B116-marinedrugs-18-00005" ref-type="bibr">116</xref>]</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">Antiviral</td><td align="left" valign="middle" rowspan="1" colspan="1">debromoaplysiatoxin (<bold>123</bold>)/cyanobacterium</td><td align="left" valign="middle" rowspan="1" colspan="1">Polyketide <sup>d</sup></td><td align="left" valign="middle" rowspan="1" colspan="1">CHIKV inhibition</td><td align="left" valign="middle" rowspan="1" colspan="1">1.4 μM</td><td align="left" valign="middle" rowspan="1" colspan="1">Undetermined</td><td align="left" valign="middle" rowspan="1" colspan="1">NZL, SGP</td><td align="left" valign="middle" rowspan="1" colspan="1">[<xref rid="B117-marinedrugs-18-00005" ref-type="bibr">117</xref>]</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">Antiviral</td><td align="left" valign="middle" rowspan="1" colspan="1">dolabelladienol A (<bold>124</bold>)/alga</td><td align="left" valign="middle" rowspan="1" colspan="1">Terpenoid <sup>e</sup></td><td align="left" valign="middle" rowspan="1" colspan="1">HIV-1 inhibition</td><td align="left" valign="middle" rowspan="1" colspan="1">2.9 μM</td><td align="left" valign="middle" rowspan="1" colspan="1">Undetermined</td><td align="left" valign="middle" rowspan="1" colspan="1">BRA, COL, ESP</td><td align="left" valign="middle" rowspan="1" colspan="1">[<xref rid="B118-marinedrugs-18-00005" ref-type="bibr">118</xref>]</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">Antiviral</td><td align="left" valign="middle" rowspan="1" colspan="1"><italic>D. plectens</italic> diterpene (<bold>125</bold>)/alga</td><td align="left" valign="middle" rowspan="1" colspan="1">Terpenoid <sup>e</sup></td><td align="left" valign="middle" rowspan="1" colspan="1">HIV-1 inhibition</td><td align="left" valign="middle" rowspan="1" colspan="1">16.1 μM</td><td align="left" valign="middle" rowspan="1" colspan="1">Undetermined</td><td align="left" valign="middle" rowspan="1" colspan="1">CHN</td><td align="left" valign="middle" rowspan="1" colspan="1">[<xref rid="B119-marinedrugs-18-00005" ref-type="bibr">119</xref>]</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">Antiviral</td><td align="left" valign="middle" rowspan="1" colspan="1"><italic>Dysidea</italic> sp. PBDEs (<bold>22</bold>, <bold>23</bold>)/sponge</td><td align="left" valign="middle" rowspan="1" colspan="1">Polyketide <sup>d</sup></td><td align="left" valign="middle" rowspan="1" colspan="1">Hepatitis B inhibition</td><td align="left" valign="middle" rowspan="1" colspan="1">0.23–0.80 μM</td><td align="left" valign="middle" rowspan="1" colspan="1">Core promoter inhibition</td><td align="left" valign="middle" rowspan="1" colspan="1">IDN, JPN, NLD</td><td align="left" valign="middle" rowspan="1" colspan="1">[<xref rid="B120-marinedrugs-18-00005" ref-type="bibr">120</xref>]</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">Antiviral</td><td align="left" valign="middle" rowspan="1" colspan="1">echrebsteroid C (<bold>126</bold>)/gorgonian</td><td align="left" valign="middle" rowspan="1" colspan="1">Terpenoid <sup>e</sup></td><td align="left" valign="middle" rowspan="1" colspan="1">RSV inhibition</td><td align="left" valign="middle" rowspan="1" colspan="1">0.19 μM</td><td align="left" valign="middle" rowspan="1" colspan="1">Undetermined</td><td align="left" valign="middle" rowspan="1" colspan="1">CHN</td><td align="left" valign="middle" rowspan="1" colspan="1">[<xref rid="B121-marinedrugs-18-00005" ref-type="bibr">121</xref>]</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">Antiviral</td><td align="left" valign="middle" rowspan="1" colspan="1">(+)-pestaloxazine A (<bold>127</bold>)/fungus</td><td align="left" valign="middle" rowspan="1" colspan="1">Alkaloid <sup>f</sup></td><td align="left" valign="middle" rowspan="1" colspan="1">Enterovirus 71 inhibition</td><td align="left" valign="middle" rowspan="1" colspan="1">14.2 μM</td><td align="left" valign="middle" rowspan="1" colspan="1">Undetermined</td><td align="left" valign="middle" rowspan="1" colspan="1">CHN</td><td align="left" valign="middle" rowspan="1" colspan="1">[<xref rid="B122-marinedrugs-18-00005" ref-type="bibr">122</xref>]</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">Antiviral </td><td align="left" valign="middle" rowspan="1" colspan="1">phlorofucofuroeckol-A(<bold>10</bold>)/alga</td><td align="left" valign="middle" rowspan="1" colspan="1">Polyketide <sup>d</sup></td><td align="left" valign="middle" rowspan="1" colspan="1">MNV inhibition</td><td align="left" valign="middle" rowspan="1" colspan="1">0.9 μM</td><td align="left" valign="middle" rowspan="1" colspan="1">Undetermined</td><td align="left" valign="middle" rowspan="1" colspan="1">S. KOR</td><td align="left" valign="middle" rowspan="1" colspan="1">[<xref rid="B123-marinedrugs-18-00005" ref-type="bibr">123</xref>]</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">Antiviral</td><td align="left" valign="middle" rowspan="1" colspan="1">secocrassumol (<bold>128</bold>)/soft coral</td><td align="left" valign="middle" rowspan="1" colspan="1">Terpenoid <sup>e</sup></td><td align="left" valign="middle" rowspan="1" colspan="1">HCMV inhibition</td><td align="left" valign="middle" rowspan="1" colspan="1">5 μg/mL</td><td align="left" valign="middle" rowspan="1" colspan="1">Undetermined</td><td align="left" valign="middle" rowspan="1" colspan="1">TWN</td><td align="left" valign="middle" rowspan="1" colspan="1">[<xref rid="B124-marinedrugs-18-00005" ref-type="bibr">124</xref>]</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">Antiviral</td><td align="left" valign="middle" rowspan="1" colspan="1">sporolide B (<bold>129</bold>)/bacterium</td><td align="left" valign="middle" rowspan="1" colspan="1">Polyketide <sup>d</sup></td><td align="left" valign="middle" rowspan="1" colspan="1">HIV-reverse transcriptase inhibition</td><td align="left" valign="middle" rowspan="1" colspan="1">14 μM</td><td align="left" valign="middle" rowspan="1" colspan="1">Undetermined</td><td align="left" valign="middle" rowspan="1" colspan="1">IND</td><td align="left" valign="middle" rowspan="1" colspan="1">[<xref rid="B125-marinedrugs-18-00005" ref-type="bibr">125</xref>]</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">Antiviral</td><td align="left" valign="middle" rowspan="1" colspan="1">stellettapeptins A and B (<bold>130</bold>, <bold>131</bold>)/sponge</td><td align="left" valign="middle" rowspan="1" colspan="1">Peptide <sup>f</sup></td><td align="left" valign="middle" rowspan="1" colspan="1">HIV-1 infection inhibition</td><td align="left" valign="middle" rowspan="1" colspan="1">23–27 nM</td><td align="left" valign="middle" rowspan="1" colspan="1">Undetermined</td><td align="left" valign="middle" rowspan="1" colspan="1">USA</td><td align="left" valign="middle" rowspan="1" colspan="1">[<xref rid="B126-marinedrugs-18-00005" ref-type="bibr">126</xref>]</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">Antiviral</td><td align="left" valign="middle" rowspan="1" colspan="1">trichobotrysin A (<bold>132</bold>)/fungus</td><td align="left" valign="middle" rowspan="1" colspan="1">Polyketide <sup>d</sup> /Alkaloid <sup>f</sup></td><td align="left" valign="middle" rowspan="1" colspan="1">HSV-1 inhibition </td><td align="left" valign="middle" rowspan="1" colspan="1">3.08 μM</td><td align="left" valign="middle" rowspan="1" colspan="1">Undetermined</td><td align="left" valign="middle" rowspan="1" colspan="1">CHN</td><td align="left" valign="middle" rowspan="1" colspan="1">[<xref rid="B127-marinedrugs-18-00005" ref-type="bibr">127</xref>]</td></tr><tr><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1"><bold>Anthelmintic</bold></td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">phorioadenine A (<bold>133</bold>)/sponge</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Alkaloid <sup>f</sup></td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1"><italic>H. contortus</italic> inhibition</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">31 μg/mL <sup>+++</sup></td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Undetermined</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">AUS</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">[<xref rid="B128-marinedrugs-18-00005" ref-type="bibr">128</xref>]</td></tr></tbody></table><table-wrap-foot><fn><p><bold><sup>a</sup> Organism</bold>: <italic>Kingdom Animalia</italic>: ascidian, flatfish, sea snakes (Phylum Chordata), gorgonian, coral (Phylum Cnidaria), sea cucumber (Phylum Echinodermata), nudibranch (Phylum Mollusca), sponge (Phylum Porifera); <italic>Kingdom Monera</italic>: bacterium (Phylum Cyanobacteria); <italic>Kingdom Fungi</italic>: fungus; <italic>Kingdom Plantae:</italic> alga, mangrove, seagrass; <italic>Kingdom Protista</italic>: dinoflagellates; <bold><sup>b</sup> IC<sub>50</sub></bold>: concentration of a compound required for 50% inhibition in vitro, *: estimated IC<sub>50</sub>, **: MIC<sub>80</sub>, MIC<sub>90</sub>, or IC<sub>90</sub>, ***: in vivo study; <sup>+</sup> MIC: minimum inhibitory concentration, <sup>++</sup> MID: minimum inhibitory concentration per disk; <sup>+++</sup> LC<sub>90</sub>: concentration of a compound required for 90% lethality; <bold><sup>b</sup> MMOA</bold>: molecular mechanism of action; <bold><sup>c</sup> Country</bold>: AUS: Australia; BEL: Belgium; BGD: Bangladesh; BRA: Brazil; CAN: Canada; CHE: Switzerland; CHN: China; COL: Colombia; CRI: Costa Rica; DEU: Germany; EGY: Egypt; ESP: Spain; FRA: France; GBR: United Kingdom; IDN: Indonesia; IND: India; IRL: Ireland; ISR: Israel; ITA: Italy; JPN: Japan; MYS: Malaysia; NLD: The Netherlands; NZL: New Zealand; PRT: Portugal; SAU: Saudi Arabia; SGP: Singapore; S. KOR: South Korea; THAI: Thailand; TWN: Taiwan; VNM: Vietnam; ZAF: S. Africa; <bold>Chemistry: <sup>d</sup></bold> polyketide; <bold><sup>e</sup></bold> terpene; <bold><sup>f</sup></bold> nitrogen-containing compound; <bold><sup>g</sup></bold> polysaccharide; <bold><sup>h</sup></bold> shikimate; <bold>Abbreviations:</bold> CHIKV: chikungunya virus; HCMV: human cytomegalovirus; MNV: murine norovirus; HSV: herpes simplex virus; ICL: isocitrate lyase; MR: methicillin-resistant; PBP2a: penicillin-binding protein 2a; RNAP: RNA-polymerase; RSV: respiratory syncytial virus; TNF-α: tumor necrosis factor α.</p></fn></table-wrap-foot></table-wrap><table-wrap id="marinedrugs-18-00005-t002" orientation="portrait" position="float"><object-id pub-id-type="pii">marinedrugs-18-00005-t002_Table 2</object-id><label>Table 2</label><caption><p>Marine pharmacology in 2014–2015: marine compounds with antidiabetic and anti-inflammatory activity, and affecting the immune and nervous system.</p></caption><table frame="hsides" rules="groups"><thead><tr><th align="left" valign="middle" style="border-top:solid thin;border-bottom:solid thin" rowspan="1" colspan="1">Drug Class</th><th align="left" valign="middle" style="border-top:solid thin;border-bottom:solid thin" rowspan="1" colspan="1">Compound/Organism <sup>a+</sup></th><th align="left" valign="middle" style="border-top:solid thin;border-bottom:solid thin" rowspan="1" colspan="1">Chemistry</th><th align="left" valign="middle" style="border-top:solid thin;border-bottom:solid thin" rowspan="1" colspan="1">Pharmacological Activity</th><th align="left" valign="middle" style="border-top:solid thin;border-bottom:solid thin" rowspan="1" colspan="1">IC<sub>50</sub><sup>b</sup></th><th align="left" valign="middle" style="border-top:solid thin;border-bottom:solid thin" rowspan="1" colspan="1">MMOA <sup>c</sup></th><th align="left" valign="middle" style="border-top:solid thin;border-bottom:solid thin" rowspan="1" colspan="1">Country <sup>d</sup></th><th align="left" valign="middle" style="border-top:solid thin;border-bottom:solid thin" rowspan="1" colspan="1">References</th></tr></thead><tbody><tr><td align="left" valign="middle" rowspan="1" colspan="1">Antidiabetic</td><td align="left" valign="middle" rowspan="1" colspan="1">fucoxanthin and fucoxanthinol (<bold>134</bold>, <bold>135</bold>)/alga</td><td align="left" valign="middle" rowspan="1" colspan="1">Terpenoid <sup>f</sup></td><td align="left" valign="middle" rowspan="1" colspan="1">Improved glucose tolerance in vitro and in vivo</td><td align="left" valign="middle" rowspan="1" colspan="1">50 µM *</td><td align="left" valign="middle" rowspan="1" colspan="1">Cytokine inhibition</td><td align="left" valign="middle" rowspan="1" colspan="1">JPN, S. KOR</td><td align="left" valign="middle" rowspan="1" colspan="1">[<xref rid="B154-marinedrugs-18-00005" ref-type="bibr">154</xref>,<xref rid="B155-marinedrugs-18-00005" ref-type="bibr">155</xref>]</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">Antidiabetic</td><td align="left" valign="middle" rowspan="1" colspan="1">octaphlorethol A (<bold>136</bold>)/alga</td><td align="left" valign="middle" rowspan="1" colspan="1">Shikimate <sup>h</sup></td><td align="left" valign="middle" rowspan="1" colspan="1">α-glucosidase inhibition</td><td align="left" valign="middle" rowspan="1" colspan="1">110 µM</td><td align="left" valign="middle" rowspan="1" colspan="1">Molecular docking on active site</td><td align="left" valign="middle" rowspan="1" colspan="1">CAN, S. KOR</td><td align="left" valign="middle" rowspan="1" colspan="1">[<xref rid="B156-marinedrugs-18-00005" ref-type="bibr">156</xref>]</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">Antidiabetic</td><td align="left" valign="middle" rowspan="1" colspan="1">phlorofucofuroeckol-A (<bold>10</bold>)/alga</td><td align="left" valign="middle" rowspan="1" colspan="1">Polyketide <sup>d</sup></td><td align="left" valign="middle" rowspan="1" colspan="1">Decreased glucose levels in vivo</td><td align="left" valign="middle" rowspan="1" colspan="1">10 mg/kg **</td><td align="left" valign="middle" rowspan="1" colspan="1">α-glucosidase inhibition</td><td align="left" valign="middle" rowspan="1" colspan="1">S. KOR</td><td align="left" valign="middle" rowspan="1" colspan="1">[<xref rid="B157-marinedrugs-18-00005" ref-type="bibr">157</xref>]</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">Antidiabetic</td><td align="left" valign="middle" rowspan="1" colspan="1">Con-Ins G1 (<bold>137</bold>)/cone snail</td><td align="left" valign="middle" rowspan="1" colspan="1">Peptide <sup>g</sup></td><td align="left" valign="middle" rowspan="1" colspan="1">Hypoglycemia induction</td><td align="left" valign="middle" rowspan="1" colspan="1">65 ng/g *</td><td align="left" valign="middle" rowspan="1" colspan="1">Undetermined</td><td align="left" valign="middle" rowspan="1" colspan="1">AUS, DNK, USA</td><td align="left" valign="middle" rowspan="1" colspan="1">[<xref rid="B158-marinedrugs-18-00005" ref-type="bibr">158</xref>]</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">Antidiabetic</td><td align="left" valign="middle" rowspan="1" colspan="1">dehydroeuryspongin A (<bold>138</bold>)/sponge </td><td align="left" valign="middle" rowspan="1" colspan="1">Terpenoid <sup>f</sup></td><td align="left" valign="middle" rowspan="1" colspan="1">PTP1B inhibition</td><td align="left" valign="middle" rowspan="1" colspan="1">3.58 μM</td><td align="left" valign="middle" rowspan="1" colspan="1">Undetermined</td><td align="left" valign="middle" rowspan="1" colspan="1">IDN, JPN</td><td align="left" valign="middle" rowspan="1" colspan="1">[<xref rid="B159-marinedrugs-18-00005" ref-type="bibr">159</xref>]</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">Antidiabetic</td><td align="left" valign="middle" rowspan="1" colspan="1"><italic>Epicoccum</italic> sp. diterpene (<bold>139</bold>)/fungus</td><td align="left" valign="middle" rowspan="1" colspan="1">Terpenoid <sup>f</sup></td><td align="left" valign="middle" rowspan="1" colspan="1">α-glucosidase inhibition</td><td align="left" valign="middle" rowspan="1" colspan="1">4.6 μM</td><td align="left" valign="middle" rowspan="1" colspan="1">Undetermined</td><td align="left" valign="middle" rowspan="1" colspan="1">CHN</td><td align="left" valign="middle" rowspan="1" colspan="1">[<xref rid="B160-marinedrugs-18-00005" ref-type="bibr">160</xref>]</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">Antidiabetic</td><td align="left" valign="middle" rowspan="1" colspan="1">suncheonoside A (<bold>140</bold>)/bacterium</td><td align="left" valign="middle" rowspan="1" colspan="1">Terpenoid <sup>f</sup></td><td align="left" valign="middle" rowspan="1" colspan="1">Adiponectin production</td><td align="left" valign="middle" rowspan="1" colspan="1">10 μM *</td><td align="left" valign="middle" rowspan="1" colspan="1">Undetermined</td><td align="left" valign="middle" rowspan="1" colspan="1">S. KOR</td><td align="left" valign="middle" rowspan="1" colspan="1">[<xref rid="B161-marinedrugs-18-00005" ref-type="bibr">161</xref>]</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">Antidiabetic</td><td align="left" valign="middle" rowspan="1" colspan="1">terrelumamide A (<bold>141</bold>)/fungus</td><td align="left" valign="middle" rowspan="1" colspan="1">Peptide <sup>g</sup></td><td align="left" valign="middle" rowspan="1" colspan="1">Adiponectin production</td><td align="left" valign="middle" rowspan="1" colspan="1">37 μM *</td><td align="left" valign="middle" rowspan="1" colspan="1">Undetermined</td><td align="left" valign="middle" rowspan="1" colspan="1">S. KOR</td><td align="left" valign="middle" rowspan="1" colspan="1">[<xref rid="B162-marinedrugs-18-00005" ref-type="bibr">162</xref>]</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">Antidiabetic</td><td align="left" valign="middle" rowspan="1" colspan="1"><italic>X. testudinaria</italic> lipid (<bold>142</bold>)/sponge</td><td align="left" valign="middle" rowspan="1" colspan="1">Polyketide <sup>d</sup></td><td align="left" valign="middle" rowspan="1" colspan="1">PTP1B inhibition</td><td align="left" valign="middle" rowspan="1" colspan="1">5.3 μM</td><td align="left" valign="middle" rowspan="1" colspan="1">Undetermined</td><td align="left" valign="middle" rowspan="1" colspan="1">CHN</td><td align="left" valign="middle" rowspan="1" colspan="1">[<xref rid="B163-marinedrugs-18-00005" ref-type="bibr">163</xref>]</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">Anti-inflammatory</td><td align="left" valign="middle" rowspan="1" colspan="1">alcyonolide congeners (<bold>143</bold>, <bold>144</bold>)/soft coral</td><td align="left" valign="middle" rowspan="1" colspan="1">Terpenoid <sup>f</sup></td><td align="left" valign="middle" rowspan="1" colspan="1">Macrophage NO inhibition</td><td align="left" valign="middle" rowspan="1" colspan="1">2 μM *</td><td align="left" valign="middle" rowspan="1" colspan="1">iNOS expression inhibition</td><td align="left" valign="middle" rowspan="1" colspan="1">JPN</td><td align="left" valign="middle" rowspan="1" colspan="1">[<xref rid="B164-marinedrugs-18-00005" ref-type="bibr">164</xref>]</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">Anti-inflammatory</td><td align="left" valign="middle" rowspan="1" colspan="1">astaxanthin (<bold>145</bold>)/alga</td><td align="left" valign="middle" rowspan="1" colspan="1">Terpenoid <sup>f</sup></td><td align="left" valign="middle" rowspan="1" colspan="1">Oxidative stress inhibition in vivo</td><td align="left" valign="middle" rowspan="1" colspan="1">10 mg/kg **</td><td align="left" valign="middle" rowspan="1" colspan="1">CAT and SOD enhancement</td><td align="left" valign="middle" rowspan="1" colspan="1">CHN</td><td align="left" valign="middle" rowspan="1" colspan="1">[<xref rid="B165-marinedrugs-18-00005" ref-type="bibr">165</xref>]</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">Anti-inflammatory</td><td align="left" valign="middle" rowspan="1" colspan="1">8,8′-bieckol (<bold>146</bold>)/alga</td><td align="left" valign="middle" rowspan="1" colspan="1">Polyketide <sup>e</sup></td><td align="left" valign="middle" rowspan="1" colspan="1">Macrophage NO and PGE<sub>2</sub> release inhibition</td><td align="left" valign="middle" rowspan="1" colspan="1">50 μM *</td><td align="left" valign="middle" rowspan="1" colspan="1">Inhibition of NFκB</td><td align="left" valign="middle" rowspan="1" colspan="1">S. KOR</td><td align="left" valign="middle" rowspan="1" colspan="1">[<xref rid="B166-marinedrugs-18-00005" ref-type="bibr">166</xref>]</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">Anti-inflammatory</td><td align="left" valign="middle" rowspan="1" colspan="1">convolutamydine A (<bold>147</bold>)/ bryozoa</td><td align="left" valign="middle" rowspan="1" colspan="1">Alkaloid <sup>g</sup></td><td align="left" valign="middle" rowspan="1" colspan="1">Formalin-induced licking behavior inhibition</td><td align="left" valign="middle" rowspan="1" colspan="1">0.01 mg/kg *</td><td align="left" valign="middle" rowspan="1" colspan="1">TNF-α, IL-6 release inhibition</td><td align="left" valign="middle" rowspan="1" colspan="1">BRA</td><td align="left" valign="middle" rowspan="1" colspan="1">[<xref rid="B167-marinedrugs-18-00005" ref-type="bibr">167</xref>]</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">Anti-inflammatory</td><td align="left" valign="middle" rowspan="1" colspan="1">capgermacrene A (<bold>148</bold>)/ soft coral</td><td align="left" valign="middle" rowspan="1" colspan="1">Terpenoid <sup>f</sup></td><td align="left" valign="middle" rowspan="1" colspan="1">Macrophage NO and IL-1β inhibition</td><td align="left" valign="middle" rowspan="1" colspan="1"><10 μg/mL *</td><td align="left" valign="middle" rowspan="1" colspan="1">iNOS expression inhibition</td><td align="left" valign="middle" rowspan="1" colspan="1">MYS, S. KOR</td><td align="left" valign="middle" rowspan="1" colspan="1">[<xref rid="B168-marinedrugs-18-00005" ref-type="bibr">168</xref>]</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">Anti-inflammatory</td><td align="left" valign="middle" rowspan="1" colspan="1">cathelicidin (<bold>4</bold>)/sea snake</td><td align="left" valign="middle" rowspan="1" colspan="1">Peptide <sup>g</sup></td><td align="left" valign="middle" rowspan="1" colspan="1">Binding of LPS to TLR4 inhibition</td><td align="left" valign="middle" rowspan="1" colspan="1">4 μg/mL *</td><td align="left" valign="middle" rowspan="1" colspan="1">Inflammatory cytokine inhibition</td><td align="left" valign="middle" rowspan="1" colspan="1">CHN</td><td align="left" valign="middle" rowspan="1" colspan="1">[<xref rid="B26-marinedrugs-18-00005" ref-type="bibr">26</xref>]</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">Anti-inflammatory</td><td align="left" valign="middle" rowspan="1" colspan="1">dactyloditerpenol acetate (<bold>149</bold>)/ sea hare</td><td align="left" valign="middle" rowspan="1" colspan="1">Terpenoid <sup>f</sup></td><td align="left" valign="middle" rowspan="1" colspan="1">LPS- activated microglia in vitro inhibition</td><td align="left" valign="middle" rowspan="1" colspan="1">0.4–1 μM</td><td align="left" valign="middle" rowspan="1" colspan="1">O<sub>2</sub><sup>-</sup> and TXB<sub>2</sub> inhibition</td><td align="left" valign="middle" rowspan="1" colspan="1">USA</td><td align="left" valign="middle" rowspan="1" colspan="1">[<xref rid="B169-marinedrugs-18-00005" ref-type="bibr">169</xref>]</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">Anti-inflammatory</td><td align="left" valign="middle" rowspan="1" colspan="1">dieckol (<bold>150</bold>)/alga</td><td align="left" valign="middle" rowspan="1" colspan="1">Shikimate <sup>h</sup></td><td align="left" valign="middle" rowspan="1" colspan="1">Macrophage iNOS transcription inhibition</td><td align="left" valign="middle" rowspan="1" colspan="1">30 μM *</td><td align="left" valign="middle" rowspan="1" colspan="1">Inhibition of NFκB and p38MAPK </td><td align="left" valign="middle" rowspan="1" colspan="1">S. KOR</td><td align="left" valign="middle" rowspan="1" colspan="1">[<xref rid="B170-marinedrugs-18-00005" ref-type="bibr">170</xref>]</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">Anti-inflammatory</td><td align="left" valign="middle" rowspan="1" colspan="1">dieckol (<bold>150</bold>)/alga</td><td align="left" valign="middle" rowspan="1" colspan="1">Shikimate <sup>h</sup></td><td align="left" valign="middle" rowspan="1" colspan="1">Human keratinocyte MDC/CCL22 inhibition</td><td align="left" valign="middle" rowspan="1" colspan="1">12.5 μM *</td><td align="left" valign="middle" rowspan="1" colspan="1">STAT1 phosphorylation inhibition</td><td align="left" valign="middle" rowspan="1" colspan="1">S. KOR</td><td align="left" valign="middle" rowspan="1" colspan="1">[<xref rid="B171-marinedrugs-18-00005" ref-type="bibr">171</xref>]</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">Anti-inflammatory</td><td align="left" valign="middle" rowspan="1" colspan="1">excavatolide B (<bold>151</bold>)/gorgonian</td><td align="left" valign="middle" rowspan="1" colspan="1">Terpenoid <sup>f</sup></td><td align="left" valign="middle" rowspan="1" colspan="1">Macrophage iNOS and COX-2 transcription inhibition</td><td align="left" valign="middle" rowspan="1" colspan="1">25 μM *</td><td align="left" valign="middle" rowspan="1" colspan="1">In vivo iNOS protein expression reduction</td><td align="left" valign="middle" rowspan="1" colspan="1">TWN</td><td align="left" valign="middle" rowspan="1" colspan="1">[<xref rid="B172-marinedrugs-18-00005" ref-type="bibr">172</xref>]</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">Anti-inflammatory</td><td align="left" valign="middle" rowspan="1" colspan="1">flexibilide (<bold>152</bold>)/soft coral</td><td align="left" valign="middle" rowspan="1" colspan="1">Terpenoid <sup>f</sup></td><td align="left" valign="middle" rowspan="1" colspan="1">Neuropathic pain inhibition</td><td align="left" valign="middle" rowspan="1" colspan="1">10 µg *</td><td align="left" valign="middle" rowspan="1" colspan="1">Upregulation of TGF-β1</td><td align="left" valign="middle" rowspan="1" colspan="1">TWN</td><td align="left" valign="middle" rowspan="1" colspan="1">[<xref rid="B173-marinedrugs-18-00005" ref-type="bibr">173</xref>]</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">Anti-inflammatory</td><td align="left" valign="middle" rowspan="1" colspan="1">fucoxanthinol (<bold>135</bold>)/alga</td><td align="left" valign="middle" rowspan="1" colspan="1">Terpenoid <sup>f</sup></td><td align="left" valign="middle" rowspan="1" colspan="1">Macrophage TNF-α and MCP-1 release inhibition</td><td align="left" valign="middle" rowspan="1" colspan="1">10 μM</td><td align="left" valign="middle" rowspan="1" colspan="1">COX-2 expression inhibition</td><td align="left" valign="middle" rowspan="1" colspan="1">JPN</td><td align="left" valign="middle" rowspan="1" colspan="1">[<xref rid="B155-marinedrugs-18-00005" ref-type="bibr">155</xref>]</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">Anti-inflammatory</td><td align="left" valign="middle" rowspan="1" colspan="1"><italic>H. fusiforme</italic> flavone (<bold>153</bold>)/ alga</td><td align="left" valign="middle" rowspan="1" colspan="1">Shikimate <sup>h</sup>/Polyketide <sup>d</sup></td><td align="left" valign="middle" rowspan="1" colspan="1">Macrophage NO and PGE<sub>2</sub> release inhibition</td><td align="left" valign="middle" rowspan="1" colspan="1">10 μg/mL *</td><td align="left" valign="middle" rowspan="1" colspan="1">iNOS, COX-2 expression inhibition</td><td align="left" valign="middle" rowspan="1" colspan="1">S. KOR</td><td align="left" valign="middle" rowspan="1" colspan="1">[<xref rid="B174-marinedrugs-18-00005" ref-type="bibr">174</xref>]</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">Anti-inflammatory</td><td align="left" valign="middle" rowspan="1" colspan="1">5β-hydroxypalisadin B (<bold>154</bold>)/alga</td><td align="left" valign="middle" rowspan="1" colspan="1">Terpenoid <sup>f</sup></td><td align="left" valign="middle" rowspan="1" colspan="1">Macrophage NO release inhibition</td><td align="left" valign="middle" rowspan="1" colspan="1">17 μM </td><td align="left" valign="middle" rowspan="1" colspan="1">Partial iNOS expression inhibition</td><td align="left" valign="middle" rowspan="1" colspan="1">LKA, MYS, S. KOR</td><td align="left" valign="middle" rowspan="1" colspan="1">[<xref rid="B175-marinedrugs-18-00005" ref-type="bibr">175</xref>]</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">Anti-inflammatory</td><td align="left" valign="middle" rowspan="1" colspan="1">glaucumolides A and B (<bold>155</bold>, <bold>156</bold>)/soft coral</td><td align="left" valign="middle" rowspan="1" colspan="1">Terpenoid <sup>f</sup></td><td align="left" valign="middle" rowspan="1" colspan="1">Neutrophil SOX and elastase inhibition</td><td align="left" valign="middle" rowspan="1" colspan="1">2.8–4 µM *</td><td align="left" valign="middle" rowspan="1" colspan="1">iNOS, COX-2 inhibition</td><td align="left" valign="middle" rowspan="1" colspan="1">TWN</td><td align="left" valign="middle" rowspan="1" colspan="1">[<xref rid="B176-marinedrugs-18-00005" ref-type="bibr">176</xref>]</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">Anti-inflammatory</td><td align="left" valign="middle" rowspan="1" colspan="1">phlorofucofuroeckol-B (<bold>157</bold>)/alga</td><td align="left" valign="middle" rowspan="1" colspan="1">Polyketide <sup>d</sup></td><td align="left" valign="middle" rowspan="1" colspan="1">Microglia activation inhibition</td><td align="left" valign="middle" rowspan="1" colspan="1">0.1 μg/mL *</td><td align="left" valign="middle" rowspan="1" colspan="1">iNOS, COX-2 inhibition</td><td align="left" valign="middle" rowspan="1" colspan="1">S. KOR</td><td align="left" valign="middle" rowspan="1" colspan="1">[<xref rid="B177-marinedrugs-18-00005" ref-type="bibr">177</xref>]</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">Anti-inflammatory</td><td align="left" valign="middle" rowspan="1" colspan="1"><italic>P. palmata</italic> lipid (<bold>158</bold>)/alga</td><td align="left" valign="middle" rowspan="1" colspan="1">Polyketide <sup>d</sup></td><td align="left" valign="middle" rowspan="1" colspan="1">Macrophage NO release inhibition</td><td align="left" valign="middle" rowspan="1" colspan="1">16.7 μM</td><td align="left" valign="middle" rowspan="1" colspan="1">iNOS expression inhibition</td><td align="left" valign="middle" rowspan="1" colspan="1">CAN</td><td align="left" valign="middle" rowspan="1" colspan="1">[<xref rid="B178-marinedrugs-18-00005" ref-type="bibr">178</xref>]</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">Anti-inflammatory</td><td align="left" valign="middle" rowspan="1" colspan="1">reduced scytonemin (<bold>159</bold>)/alga</td><td align="left" valign="middle" rowspan="1" colspan="1">Alkaloid <sup>g</sup></td><td align="left" valign="middle" rowspan="1" colspan="1">Macrophage NO release inhibition</td><td align="left" valign="middle" rowspan="1" colspan="1">1 µM *</td><td align="left" valign="middle" rowspan="1" colspan="1">HO-1 expression induction</td><td align="left" valign="middle" rowspan="1" colspan="1">JPN</td><td align="left" valign="middle" rowspan="1" colspan="1">[<xref rid="B179-marinedrugs-18-00005" ref-type="bibr">179</xref>]</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">Anti-inflammatory</td><td align="left" valign="middle" rowspan="1" colspan="1">sinuleptolide (<bold>160</bold>)/soft coral</td><td align="left" valign="middle" rowspan="1" colspan="1">Terpenoid <sup>f</sup></td><td align="left" valign="middle" rowspan="1" colspan="1">LPS-activated rat microglia in vitro inhibition</td><td align="left" valign="middle" rowspan="1" colspan="1">0.5–2.9 μM</td><td align="left" valign="middle" rowspan="1" colspan="1">Cytokine release inhibition</td><td align="left" valign="middle" rowspan="1" colspan="1">ESP, FIN, IND, ITA, </td><td align="left" valign="middle" rowspan="1" colspan="1">[<xref rid="B180-marinedrugs-18-00005" ref-type="bibr">180</xref>]</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">Anti-inflammatory</td><td align="left" valign="middle" rowspan="1" colspan="1">sarcopanol A (<bold>161</bold>)/soft coral</td><td align="left" valign="middle" rowspan="1" colspan="1">Terpenoid <sup>f</sup></td><td align="left" valign="middle" rowspan="1" colspan="1">iNOS, COX-2, and ICAM-1 transcription inhibition</td><td align="left" valign="middle" rowspan="1" colspan="1">8.3 µM </td><td align="left" valign="middle" rowspan="1" colspan="1">NFκB inhibition</td><td align="left" valign="middle" rowspan="1" colspan="1">S. KOR, VNM</td><td align="left" valign="middle" rowspan="1" colspan="1">[<xref rid="B181-marinedrugs-18-00005" ref-type="bibr">181</xref>]</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">Anti-inflammatory</td><td align="left" valign="middle" rowspan="1" colspan="1">sinumaximol H (<bold>162</bold>)/sponge</td><td align="left" valign="middle" rowspan="1" colspan="1">Terpenoid <sup>f</sup></td><td align="left" valign="middle" rowspan="1" colspan="1">iNOS and ICAM-1 transcription inhibition</td><td align="left" valign="middle" rowspan="1" colspan="1">1 µM *</td><td align="left" valign="middle" rowspan="1" colspan="1">NFκB inhibition</td><td align="left" valign="middle" rowspan="1" colspan="1">S. KOR, VNM</td><td align="left" valign="middle" rowspan="1" colspan="1">[<xref rid="B182-marinedrugs-18-00005" ref-type="bibr">182</xref>]</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">Anti-inflammatory</td><td align="left" valign="middle" rowspan="1" colspan="1">tanzawaic acid A (<bold>163</bold>)/fungus</td><td align="left" valign="middle" rowspan="1" colspan="1">Polyketide <sup>d</sup></td><td align="left" valign="middle" rowspan="1" colspan="1">NO inhibition</td><td align="left" valign="middle" rowspan="1" colspan="1">7.1 µM</td><td align="left" valign="middle" rowspan="1" colspan="1">iNOS and PTP1B inhibition</td><td align="left" valign="middle" rowspan="1" colspan="1">VNM, S. KOR</td><td align="left" valign="middle" rowspan="1" colspan="1">[<xref rid="B183-marinedrugs-18-00005" ref-type="bibr">183</xref>]</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">Anti-inflammatory</td><td align="left" valign="middle" rowspan="1" colspan="1">aspertetranone D (<bold>164</bold>)/fungus</td><td align="left" valign="middle" rowspan="1" colspan="1">Terpenoid <sup>f</sup></td><td align="left" valign="middle" rowspan="1" colspan="1">IL-6 inhibition</td><td align="left" valign="middle" rowspan="1" colspan="1">40 µM *</td><td align="left" valign="middle" rowspan="1" colspan="1">Undetermined</td><td align="left" valign="middle" rowspan="1" colspan="1">CHN, USA</td><td align="left" valign="middle" rowspan="1" colspan="1">[<xref rid="B184-marinedrugs-18-00005" ref-type="bibr">184</xref>]</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">Anti-inflammatory</td><td align="left" valign="middle" rowspan="1" colspan="1">briarenolide J (<bold>165</bold>)/soft coral</td><td align="left" valign="middle" rowspan="1" colspan="1">Terpenoid <sup>f</sup></td><td align="left" valign="middle" rowspan="1" colspan="1">Neutrophil SOX and elastase inhibition</td><td align="left" valign="middle" rowspan="1" colspan="1">10–15 µM</td><td align="left" valign="middle" rowspan="1" colspan="1">Undetermined</td><td align="left" valign="middle" rowspan="1" colspan="1">TWN</td><td align="left" valign="middle" rowspan="1" colspan="1">[<xref rid="B185-marinedrugs-18-00005" ref-type="bibr">185</xref>]</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">Anti-inflammatory</td><td align="left" valign="middle" rowspan="1" colspan="1">briarenolides K and L (<bold>166</bold>, <bold>167</bold>)/soft coral</td><td align="left" valign="middle" rowspan="1" colspan="1">Terpenoid <sup>f</sup></td><td align="left" valign="middle" rowspan="1" colspan="1">Macrophage iNOS inhibition</td><td align="left" valign="middle" rowspan="1" colspan="1">>10 μg/mL *</td><td align="left" valign="middle" rowspan="1" colspan="1">Undetermined</td><td align="left" valign="middle" rowspan="1" colspan="1">TWN</td><td align="left" valign="middle" rowspan="1" colspan="1">[<xref rid="B186-marinedrugs-18-00005" ref-type="bibr">186</xref>]</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">Anti-inflammatory</td><td align="left" valign="middle" rowspan="1" colspan="1">briarenolides U, V, W (<bold>168</bold>, <bold>169</bold>)/soft coral</td><td align="left" valign="middle" rowspan="1" colspan="1">Terpenoid <sup>f</sup></td><td align="left" valign="middle" rowspan="1" colspan="1">Macrophage COX-2 and iNOS expression inhibition</td><td align="left" valign="middle" rowspan="1" colspan="1">>10 μg/mL *</td><td align="left" valign="middle" rowspan="1" colspan="1">Undetermined</td><td align="left" valign="middle" rowspan="1" colspan="1">TWN</td><td align="left" valign="middle" rowspan="1" colspan="1">[<xref rid="B187-marinedrugs-18-00005" ref-type="bibr">187</xref>]</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">Anti-inflammatory</td><td align="left" valign="middle" rowspan="1" colspan="1">briaviolides E and I (<bold>170</bold>, <bold>171</bold>)/soft coral</td><td align="left" valign="middle" rowspan="1" colspan="1">Terpenoid <sup>f</sup></td><td align="left" valign="middle" rowspan="1" colspan="1">Neutrophil SOX and elastase inhibition</td><td align="left" valign="middle" rowspan="1" colspan="1">>10 μg/mL *</td><td align="left" valign="middle" rowspan="1" colspan="1">Undetermined</td><td align="left" valign="middle" rowspan="1" colspan="1">TWN</td><td align="left" valign="middle" rowspan="1" colspan="1">[<xref rid="B188-marinedrugs-18-00005" ref-type="bibr">188</xref>]</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">Anti-inflammatory</td><td align="left" valign="middle" rowspan="1" colspan="1">dermacozine H (<bold>172</bold>)/bacterium</td><td align="left" valign="middle" rowspan="1" colspan="1">Alkaloid <sup>g</sup></td><td align="left" valign="middle" rowspan="1" colspan="1">Radical scavenging activity</td><td align="left" valign="middle" rowspan="1" colspan="1">18.8 µM</td><td align="left" valign="middle" rowspan="1" colspan="1">Undetermined</td><td align="left" valign="middle" rowspan="1" colspan="1">DEU, EGY, UK</td><td align="left" valign="middle" rowspan="1" colspan="1">[<xref rid="B189-marinedrugs-18-00005" ref-type="bibr">189</xref>]</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">Anti-inflammatory</td><td align="left" valign="middle" rowspan="1" colspan="1">dysifragilone A (<bold>173</bold>)/sponge</td><td align="left" valign="middle" rowspan="1" colspan="1">Terpenoid <sup>f</sup></td><td align="left" valign="middle" rowspan="1" colspan="1">Macrophage NO release inhibition</td><td align="left" valign="middle" rowspan="1" colspan="1">6.6 µM</td><td align="left" valign="middle" rowspan="1" colspan="1">Undetermined</td><td align="left" valign="middle" rowspan="1" colspan="1">CHN</td><td align="left" valign="middle" rowspan="1" colspan="1">[<xref rid="B190-marinedrugs-18-00005" ref-type="bibr">190</xref>]</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">Anti-inflammatory</td><td align="left" valign="middle" rowspan="1" colspan="1"><italic>D. plectens</italic> xenicane (<bold>174</bold>)/alga</td><td align="left" valign="middle" rowspan="1" colspan="1">Terpenoid <sup>f</sup></td><td align="left" valign="middle" rowspan="1" colspan="1">Macrophage NO release inhibition</td><td align="left" valign="middle" rowspan="1" colspan="1">10 µM</td><td align="left" valign="middle" rowspan="1" colspan="1">Undetermined</td><td align="left" valign="middle" rowspan="1" colspan="1">CHN</td><td align="left" valign="middle" rowspan="1" colspan="1">[<xref rid="B191-marinedrugs-18-00005" ref-type="bibr">191</xref>]</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">Anti-inflammatory</td><td align="left" valign="middle" rowspan="1" colspan="1">comaparvin (<bold>175</bold>)/crinoid</td><td align="left" valign="middle" rowspan="1" colspan="1">Polyketide <sup>d</sup></td><td align="left" valign="middle" rowspan="1" colspan="1">Carrageenan-induced hyperalgesia inhibition</td><td align="left" valign="middle" rowspan="1" colspan="1">30 mg/kg *</td><td align="left" valign="middle" rowspan="1" colspan="1">iNOS expression inhibition</td><td align="left" valign="middle" rowspan="1" colspan="1">TWN</td><td align="left" valign="middle" rowspan="1" colspan="1">[<xref rid="B192-marinedrugs-18-00005" ref-type="bibr">192</xref>]</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">Anti-inflammatory</td><td align="left" valign="middle" rowspan="1" colspan="1">hirsutalins N and S (<bold>176</bold>, <bold>177</bold>)/ soft coral</td><td align="left" valign="middle" rowspan="1" colspan="1">Terpenoid <sup>f</sup></td><td align="left" valign="middle" rowspan="1" colspan="1">Neutrophil elastase inhibition</td><td align="left" valign="middle" rowspan="1" colspan="1">10 μM *</td><td align="left" valign="middle" rowspan="1" colspan="1">Undetermined</td><td align="left" valign="middle" rowspan="1" colspan="1">TWN</td><td align="left" valign="middle" rowspan="1" colspan="1">[<xref rid="B193-marinedrugs-18-00005" ref-type="bibr">193</xref>,<xref rid="B194-marinedrugs-18-00005" ref-type="bibr">194</xref>]</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">Anti-inflammatory</td><td align="left" valign="middle" rowspan="1" colspan="1">hirsutocospiro A (<bold>178</bold>)/soft coral</td><td align="left" valign="middle" rowspan="1" colspan="1">Terpenoid <sup>f</sup></td><td align="left" valign="middle" rowspan="1" colspan="1">Neutrophil SOX and elastase inhibition</td><td align="left" valign="middle" rowspan="1" colspan="1">3.7–4.1 μM</td><td align="left" valign="middle" rowspan="1" colspan="1">Undetermined</td><td align="left" valign="middle" rowspan="1" colspan="1">TWN</td><td align="left" valign="middle" rowspan="1" colspan="1">[<xref rid="B195-marinedrugs-18-00005" ref-type="bibr">195</xref>]</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">Anti-inflammatory</td><td align="left" valign="middle" rowspan="1" colspan="1">isosinulaflexiolide K (<bold>179</bold>)/soft coral</td><td align="left" valign="middle" rowspan="1" colspan="1">Terpenoid <sup>f</sup></td><td align="left" valign="middle" rowspan="1" colspan="1">Macrophage COX-2 and iNOS expression inhibition</td><td align="left" valign="middle" rowspan="1" colspan="1">>10 μM *</td><td align="left" valign="middle" rowspan="1" colspan="1">Undetermined</td><td align="left" valign="middle" rowspan="1" colspan="1">TWN</td><td align="left" valign="middle" rowspan="1" colspan="1">[<xref rid="B196-marinedrugs-18-00005" ref-type="bibr">196</xref>]</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">Anti-inflammatory</td><td align="left" valign="middle" rowspan="1" colspan="1">klyflaccisteroid F (<bold>180</bold>)/soft coral</td><td align="left" valign="middle" rowspan="1" colspan="1">Terpenoid <sup>f</sup></td><td align="left" valign="middle" rowspan="1" colspan="1">Neutrophil SOX and elastase inhibition</td><td align="left" valign="middle" rowspan="1" colspan="1">0.34 μM </td><td align="left" valign="middle" rowspan="1" colspan="1">Undetermined</td><td align="left" valign="middle" rowspan="1" colspan="1">TWN</td><td align="left" valign="middle" rowspan="1" colspan="1">[<xref rid="B197-marinedrugs-18-00005" ref-type="bibr">197</xref>]</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">Anti-inflammatory</td><td align="left" valign="middle" rowspan="1" colspan="1">krempfielin N (<bold>181</bold>)/soft coral</td><td align="left" valign="middle" rowspan="1" colspan="1">Terpenoid <sup>f</sup></td><td align="left" valign="middle" rowspan="1" colspan="1">Neutrophil SOX and elastase inhibition</td><td align="left" valign="middle" rowspan="1" colspan="1">>10 μM *</td><td align="left" valign="middle" rowspan="1" colspan="1">Undetermined</td><td align="left" valign="middle" rowspan="1" colspan="1">TWN</td><td align="left" valign="middle" rowspan="1" colspan="1">[<xref rid="B198-marinedrugs-18-00005" ref-type="bibr">198</xref>]</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">Anti-inflammatory</td><td align="left" valign="middle" rowspan="1" colspan="1">krempfielins Q and R (<bold>182</bold>, <bold>183</bold>)/soft coral</td><td align="left" valign="middle" rowspan="1" colspan="1">Terpenoid <sup>f</sup></td><td align="left" valign="middle" rowspan="1" colspan="1">Neutrophil SOX and elastase inhibition</td><td align="left" valign="middle" rowspan="1" colspan="1">>10 μM *</td><td align="left" valign="middle" rowspan="1" colspan="1">Undetermined</td><td align="left" valign="middle" rowspan="1" colspan="1">TWN</td><td align="left" valign="middle" rowspan="1" colspan="1">[<xref rid="B199-marinedrugs-18-00005" ref-type="bibr">199</xref>]</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">Anti-inflammatory</td><td align="left" valign="middle" rowspan="1" colspan="1">methylfarnesylquinone (<bold>184</bold>)/alga</td><td align="left" valign="middle" rowspan="1" colspan="1">Shikimate <sup>h</sup>/Terpenoid <sup>f</sup></td><td align="left" valign="middle" rowspan="1" colspan="1">Neutrophil SOX and elastase inhibition</td><td align="left" valign="middle" rowspan="1" colspan="1">0.2–0.48 µg/mL</td><td align="left" valign="middle" rowspan="1" colspan="1">Undetermined</td><td align="left" valign="middle" rowspan="1" colspan="1">TWN</td><td align="left" valign="middle" rowspan="1" colspan="1">[<xref rid="B200-marinedrugs-18-00005" ref-type="bibr">200</xref>]</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">Anti-inflammatory</td><td align="left" valign="middle" rowspan="1" colspan="1">monanchosterol B (<bold>185</bold>)/sponge</td><td align="left" valign="middle" rowspan="1" colspan="1">Terpenoid <sup>f</sup></td><td align="left" valign="middle" rowspan="1" colspan="1">Macrophage IL-6 expression inhibition</td><td align="left" valign="middle" rowspan="1" colspan="1">5 µM</td><td align="left" valign="middle" rowspan="1" colspan="1">Undetermined</td><td align="left" valign="middle" rowspan="1" colspan="1">S. KOR </td><td align="left" valign="middle" rowspan="1" colspan="1">[<xref rid="B201-marinedrugs-18-00005" ref-type="bibr">201</xref>]</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">Anti-inflammatory</td><td align="left" valign="middle" rowspan="1" colspan="1"><italic>P. nodosus</italic> sterol (<bold>186</bold>)/starfish </td><td align="left" valign="middle" rowspan="1" colspan="1">Terpenoid <sup>f</sup></td><td align="left" valign="middle" rowspan="1" colspan="1">IL-12 and IL-6 inhibition</td><td align="left" valign="middle" rowspan="1" colspan="1">1.3–3.1 µM</td><td align="left" valign="middle" rowspan="1" colspan="1">Undetermined</td><td align="left" valign="middle" rowspan="1" colspan="1">VNM, S. KOR</td><td align="left" valign="middle" rowspan="1" colspan="1">[<xref rid="B202-marinedrugs-18-00005" ref-type="bibr">202</xref>] </td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">Anti-inflammatory</td><td align="left" valign="middle" rowspan="1" colspan="1">rhytidenone C (<bold>187</bold>)/fungus</td><td align="left" valign="middle" rowspan="1" colspan="1">Polyketide <sup>d</sup></td><td align="left" valign="middle" rowspan="1" colspan="1">Macrophage NO inhibition</td><td align="left" valign="middle" rowspan="1" colspan="1">0.31 µM</td><td align="left" valign="middle" rowspan="1" colspan="1">Undetermined</td><td align="left" valign="middle" rowspan="1" colspan="1">THA</td><td align="left" valign="middle" rowspan="1" colspan="1">[<xref rid="B203-marinedrugs-18-00005" ref-type="bibr">203</xref>]</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">Anti-inflammatory</td><td align="left" valign="middle" rowspan="1" colspan="1">sarcocrassocolide E (<bold>188</bold>)/soft coral</td><td align="left" valign="middle" rowspan="1" colspan="1">Terpenoid <sup>f</sup></td><td align="left" valign="middle" rowspan="1" colspan="1">Macrophage COX-2 and iNOS expression inhibition</td><td align="left" valign="middle" rowspan="1" colspan="1"><10 μM *</td><td align="left" valign="middle" rowspan="1" colspan="1">Undetermined</td><td align="left" valign="middle" rowspan="1" colspan="1">TWN</td><td align="left" valign="middle" rowspan="1" colspan="1">[<xref rid="B204-marinedrugs-18-00005" ref-type="bibr">204</xref>]</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">Anti-inflammatory</td><td align="left" valign="middle" rowspan="1" colspan="1">sinulacembranolide A (<bold>189</bold>)/octocoral</td><td align="left" valign="middle" rowspan="1" colspan="1">Terpenoid <sup>f</sup></td><td align="left" valign="middle" rowspan="1" colspan="1">Macrophage iNOS expression inhibition</td><td align="left" valign="middle" rowspan="1" colspan="1"><10 μM</td><td align="left" valign="middle" rowspan="1" colspan="1">Undetermined</td><td align="left" valign="middle" rowspan="1" colspan="1">TWN</td><td align="left" valign="middle" rowspan="1" colspan="1">[<xref rid="B205-marinedrugs-18-00005" ref-type="bibr">205</xref>]</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">Anti-inflammatory</td><td align="left" valign="middle" rowspan="1" colspan="1">thomimarine B (<bold>190</bold>)/fungus</td><td align="left" valign="middle" rowspan="1" colspan="1">Terpenoid <sup>f</sup></td><td align="left" valign="middle" rowspan="1" colspan="1">Macrophage NO inhibition</td><td align="left" valign="middle" rowspan="1" colspan="1">>10 μM</td><td align="left" valign="middle" rowspan="1" colspan="1">Undetermined</td><td align="left" valign="middle" rowspan="1" colspan="1">RUS, VNM</td><td align="left" valign="middle" rowspan="1" colspan="1">[<xref rid="B206-marinedrugs-18-00005" ref-type="bibr">206</xref>]</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">Anti-inflammatory</td><td align="left" valign="middle" rowspan="1" colspan="1">tortuosene A (<bold>191</bold>)/soft coral</td><td align="left" valign="middle" rowspan="1" colspan="1">Terpenoid <sup>f</sup></td><td align="left" valign="middle" rowspan="1" colspan="1">Neutrophil SOX inhibition</td><td align="left" valign="middle" rowspan="1" colspan="1">7.3 μM</td><td align="left" valign="middle" rowspan="1" colspan="1">Undetermined</td><td align="left" valign="middle" rowspan="1" colspan="1">TWN</td><td align="left" valign="middle" rowspan="1" colspan="1">[<xref rid="B207-marinedrugs-18-00005" ref-type="bibr">207</xref>]</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">Immune system</td><td align="left" valign="middle" rowspan="1" colspan="1">grassypeptolide A (<bold>192</bold>)/cyanobacterium</td><td align="left" valign="middle" rowspan="1" colspan="1">Peptide <sup>g</sup></td><td align="left" valign="middle" rowspan="1" colspan="1">IL-2 and T-cell proliferation inhibition</td><td align="left" valign="middle" rowspan="1" colspan="1">1 μM *</td><td align="left" valign="middle" rowspan="1" colspan="1">Dipeptidyl peptidase 8 inhibition</td><td align="left" valign="middle" rowspan="1" colspan="1">CHN, JPN, USA</td><td align="left" valign="middle" rowspan="1" colspan="1">[<xref rid="B208-marinedrugs-18-00005" ref-type="bibr">208</xref>]</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">Immune system</td><td align="left" valign="middle" rowspan="1" colspan="1"><italic>F. reticulata</italic> alkaloids (<bold>193</bold>)/sponge</td><td align="left" valign="middle" rowspan="1" colspan="1">Alkaloid <sup>g</sup></td><td align="left" valign="middle" rowspan="1" colspan="1">IL-2 inhibition</td><td align="left" valign="middle" rowspan="1" colspan="1">5–50 µM *</td><td align="left" valign="middle" rowspan="1" colspan="1">Undetermined</td><td align="left" valign="middle" rowspan="1" colspan="1">CHN, NLD</td><td align="left" valign="middle" rowspan="1" colspan="1">[<xref rid="B209-marinedrugs-18-00005" ref-type="bibr">209</xref>]</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">Immune system</td><td align="left" valign="middle" rowspan="1" colspan="1">luzonicoside A (<bold>194</bold>)/starfish</td><td align="left" valign="middle" rowspan="1" colspan="1">Terpenoid <sup>f</sup></td><td align="left" valign="middle" rowspan="1" colspan="1">Macrophage NO and ROS stimulation</td><td align="left" valign="middle" rowspan="1" colspan="1">0.01–0.1 µM *</td><td align="left" valign="middle" rowspan="1" colspan="1">Undetermined</td><td align="left" valign="middle" rowspan="1" colspan="1">RUS, VNM</td><td align="left" valign="middle" rowspan="1" colspan="1">[<xref rid="B210-marinedrugs-18-00005" ref-type="bibr">210</xref>]</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">Immune system</td><td align="left" valign="middle" rowspan="1" colspan="1">typicoside C1(<bold>195</bold>)/sea cucumber</td><td align="left" valign="middle" rowspan="1" colspan="1">Terpenoid <sup>f</sup></td><td align="left" valign="middle" rowspan="1" colspan="1">Macrophage ROS stimulation</td><td align="left" valign="middle" rowspan="1" colspan="1"><1 ng/mL *</td><td align="left" valign="middle" rowspan="1" colspan="1">Undetermined</td><td align="left" valign="middle" rowspan="1" colspan="1">IND, RUS</td><td align="left" valign="middle" rowspan="1" colspan="1">[<xref rid="B211-marinedrugs-18-00005" ref-type="bibr">211</xref>]</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1"><bold>Nervous system</bold></td><td align="left" valign="middle" rowspan="1" colspan="1">aurone glycoside (<bold>196</bold>)/fungus</td><td align="left" valign="middle" rowspan="1" colspan="1">Shikimate <sup>h</sup>/Polyketide <sup>d</sup></td><td align="left" valign="middle" rowspan="1" colspan="1">Oxidative stress neuroprotection</td><td align="left" valign="middle" rowspan="1" colspan="1">1 µM *</td><td align="left" valign="middle" rowspan="1" colspan="1">Apoptosis inhibition </td><td align="left" valign="middle" rowspan="1" colspan="1">CHN</td><td align="left" valign="middle" rowspan="1" colspan="1">[<xref rid="B212-marinedrugs-18-00005" ref-type="bibr">212</xref>]</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">Nervous system</td><td align="left" valign="middle" rowspan="1" colspan="1">azaspiracid-1 (<bold>197</bold>)/alga</td><td align="left" valign="middle" rowspan="1" colspan="1">Polyketide <sup>d</sup>/<break></break>Alkaloid <sup>g</sup></td><td align="left" valign="middle" rowspan="1" colspan="1">Peripherin-labelled neurite process</td><td align="left" valign="middle" rowspan="1" colspan="1">15 nM *</td><td align="left" valign="middle" rowspan="1" colspan="1">Peripherin isoform downregulation</td><td align="left" valign="middle" rowspan="1" colspan="1">NOR</td><td align="left" valign="middle" rowspan="1" colspan="1">[<xref rid="B213-marinedrugs-18-00005" ref-type="bibr">213</xref>]</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">Nervous system</td><td align="left" valign="middle" rowspan="1" colspan="1">caulerpine (<bold>198</bold>)/alga</td><td align="left" valign="middle" rowspan="1" colspan="1">Alkaloid <sup>g</sup></td><td align="left" valign="middle" rowspan="1" colspan="1">Antinociceptive activity</td><td align="left" valign="middle" rowspan="1" colspan="1">40 mg/kg *</td><td align="left" valign="middle" rowspan="1" colspan="1">Involves α2 and 5-HT<sub>3</sub> receptors</td><td align="left" valign="middle" rowspan="1" colspan="1">BRA</td><td align="left" valign="middle" rowspan="1" colspan="1">[<xref rid="B214-marinedrugs-18-00005" ref-type="bibr">214</xref>]</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">Nervous systema</td><td align="left" valign="middle" rowspan="1" colspan="1">6-bromohypaphorine (<bold>199</bold>)/sea slug</td><td align="left" valign="middle" rowspan="1" colspan="1">Alkaloid <sup>g</sup></td><td align="left" valign="middle" rowspan="1" colspan="1">Human α7 nAChR agonist</td><td align="left" valign="middle" rowspan="1" colspan="1">23 µM</td><td align="left" valign="middle" rowspan="1" colspan="1">Rise [Ca<sup>2+</sup> ]i</td><td align="left" valign="middle" rowspan="1" colspan="1">RUS</td><td align="left" valign="middle" rowspan="1" colspan="1">[<xref rid="B215-marinedrugs-18-00005" ref-type="bibr">215</xref>]</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">Nervous system</td><td align="left" valign="middle" rowspan="1" colspan="1">piscidin (<bold>200</bold>)/fish</td><td align="left" valign="middle" rowspan="1" colspan="1">Peptide <sup>g</sup></td><td align="left" valign="middle" rowspan="1" colspan="1">Antinociceptive activity</td><td align="left" valign="middle" rowspan="1" colspan="1">20 µg/rat *</td><td align="left" valign="middle" rowspan="1" colspan="1">Phosphor-mTOR inhibition</td><td align="left" valign="middle" rowspan="1" colspan="1">TWN</td><td align="left" valign="middle" rowspan="1" colspan="1">[<xref rid="B216-marinedrugs-18-00005" ref-type="bibr">216</xref>]</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">Nervous system</td><td align="left" valign="middle" rowspan="1" colspan="1"><italic>C. marmoreus</italic> conotoxin Mr1.7 (<bold>201</bold>)/cone snail</td><td align="left" valign="middle" rowspan="1" colspan="1">Peptide <sup>g</sup></td><td align="left" valign="middle" rowspan="1" colspan="1">Ach-evoked membrane current inhibition</td><td align="left" valign="middle" rowspan="1" colspan="1">53.1 nM</td><td align="left" valign="middle" rowspan="1" colspan="1">A3β2 nAChR inhibition</td><td align="left" valign="middle" rowspan="1" colspan="1">CHN</td><td align="left" valign="middle" rowspan="1" colspan="1">[<xref rid="B217-marinedrugs-18-00005" ref-type="bibr">217</xref>] </td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">Nervous system</td><td align="left" valign="middle" rowspan="1" colspan="1"><italic>C. litteratus</italic> conotoxin lt16a (<bold>202</bold>)/cone snail</td><td align="left" valign="middle" rowspan="1" colspan="1">Peptide <sup>g</sup></td><td align="left" valign="middle" rowspan="1" colspan="1">Neuronal Na<sup>+</sup> current inhibition</td><td align="left" valign="middle" rowspan="1" colspan="1">1 µM *</td><td align="left" valign="middle" rowspan="1" colspan="1">Undetermined</td><td align="left" valign="middle" rowspan="1" colspan="1">CHN</td><td align="left" valign="middle" rowspan="1" colspan="1">[<xref rid="B218-marinedrugs-18-00005" ref-type="bibr">218</xref>]</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">Nervous system</td><td align="left" valign="middle" rowspan="1" colspan="1"><italic>C. vitulinus</italic> peptide (<bold>203</bold>)/ cone snail</td><td align="left" valign="middle" rowspan="1" colspan="1">Peptide <sup>g</sup></td><td align="left" valign="middle" rowspan="1" colspan="1">Neuronal BK channel inhibition</td><td align="left" valign="middle" rowspan="1" colspan="1">8.5 µM</td><td align="left" valign="middle" rowspan="1" colspan="1">Electrostatic interaction with β4 subunits</td><td align="left" valign="middle" rowspan="1" colspan="1">CHN, USA</td><td align="left" valign="middle" rowspan="1" colspan="1">[<xref rid="B219-marinedrugs-18-00005" ref-type="bibr">219</xref>]</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">Nervous system</td><td align="left" valign="middle" rowspan="1" colspan="1">echinochrome A (<bold>204</bold>)/sea urchin</td><td align="left" valign="middle" rowspan="1" colspan="1">Polyketide <sup>d</sup></td><td align="left" valign="middle" rowspan="1" colspan="1">Acetylcholinesterase inhibition and NO scavenging</td><td align="left" valign="middle" rowspan="1" colspan="1">16.4 µM</td><td align="left" valign="middle" rowspan="1" colspan="1">Irreversible and uncompetitive inhibition</td><td align="left" valign="middle" rowspan="1" colspan="1">S. KOR, RUS</td><td align="left" valign="middle" rowspan="1" colspan="1">[<xref rid="B220-marinedrugs-18-00005" ref-type="bibr">220</xref>]</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">Nervous system</td><td align="left" valign="middle" rowspan="1" colspan="1">ganglioside LLG-3 (<bold>205</bold>)/starfish</td><td align="left" valign="middle" rowspan="1" colspan="1">Glycolipid</td><td align="left" valign="middle" rowspan="1" colspan="1">Neuritogenesis stimulation in vitro</td><td align="left" valign="middle" rowspan="1" colspan="1">1 nM *</td><td align="left" valign="middle" rowspan="1" colspan="1">MAPK signaling stimulation</td><td align="left" valign="middle" rowspan="1" colspan="1">JPN</td><td align="left" valign="middle" rowspan="1" colspan="1">[<xref rid="B221-marinedrugs-18-00005" ref-type="bibr">221</xref>]</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">Nervous system</td><td align="left" valign="middle" rowspan="1" colspan="1">heteronemin (<bold>206</bold>)/sponge</td><td align="left" valign="middle" rowspan="1" colspan="1">Terpenoid <sup>f</sup></td><td align="left" valign="middle" rowspan="1" colspan="1">TDP-43 binding to DNA inhibition</td><td align="left" valign="middle" rowspan="1" colspan="1">10.1 nM</td><td align="left" valign="middle" rowspan="1" colspan="1">Promoted aggregation of insoluble TDP-43</td><td align="left" valign="middle" rowspan="1" colspan="1">ITA</td><td align="left" valign="middle" rowspan="1" colspan="1">[<xref rid="B222-marinedrugs-18-00005" ref-type="bibr">222</xref>]</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">Nervous system</td><td align="left" valign="middle" rowspan="1" colspan="1">pinnatoxin A (<bold>207</bold>)/mollusc</td><td align="left" valign="middle" rowspan="1" colspan="1">Polyketide <sup>d</sup>/<break></break>Alkaloid <sup>g</sup></td><td align="left" valign="middle" rowspan="1" colspan="1">Muscle and neuronal nAChRs receptor inhibition</td><td align="left" valign="middle" rowspan="1" colspan="1">0.086–47.5 nM </td><td align="left" valign="middle" rowspan="1" colspan="1">EF-ketal ring confers nAChR subtype specificity</td><td align="left" valign="middle" rowspan="1" colspan="1">FRA, USA</td><td align="left" valign="middle" rowspan="1" colspan="1">[<xref rid="B223-marinedrugs-18-00005" ref-type="bibr">223</xref>]</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">Nervous tissue</td><td align="left" valign="middle" rowspan="1" colspan="1">PhcrTx1 (<bold>208</bold>)/sea anemone</td><td align="left" valign="middle" rowspan="1" colspan="1">Peptide <sup>g</sup></td><td align="left" valign="middle" rowspan="1" colspan="1">ASIC inhibition</td><td align="left" valign="middle" rowspan="1" colspan="1">100 nM</td><td align="left" valign="middle" rowspan="1" colspan="1">Lower potency on Kv channels</td><td align="left" valign="middle" rowspan="1" colspan="1">BEL, BRA, CUB, DEU, ESP, MEX </td><td align="left" valign="middle" rowspan="1" colspan="1">[<xref rid="B224-marinedrugs-18-00005" ref-type="bibr">224</xref>]</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">Nervous tissue</td><td align="left" valign="middle" rowspan="1" colspan="1">phlorofucofuroeckol-A (<bold>10</bold>)/alga</td><td align="left" valign="middle" rowspan="1" colspan="1">Polyketide <sup>d</sup></td><td align="left" valign="middle" rowspan="1" colspan="1">Butyrylcholinesterase inhibition</td><td align="left" valign="middle" rowspan="1" colspan="1">0.95 µM</td><td align="left" valign="middle" rowspan="1" colspan="1">β-secretase inhibition</td><td align="left" valign="middle" rowspan="1" colspan="1">S. KOR</td><td align="left" valign="middle" rowspan="1" colspan="1">[<xref rid="B225-marinedrugs-18-00005" ref-type="bibr">225</xref>]</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">Nervous tissue</td><td align="left" valign="middle" rowspan="1" colspan="1"><italic>S. auritum</italic> ceramide (<bold>209</bold>)/soft coral</td><td align="left" valign="middle" rowspan="1" colspan="1">Polyketide <sup>d</sup></td><td align="left" valign="middle" rowspan="1" colspan="1">Anxiolytic and CNS depressing activity in vivo</td><td align="left" valign="middle" rowspan="1" colspan="1">1 mg/kg **</td><td align="left" valign="middle" rowspan="1" colspan="1">GABA(A) receptor modulation</td><td align="left" valign="middle" rowspan="1" colspan="1">EGY, USA</td><td align="left" valign="middle" rowspan="1" colspan="1">[<xref rid="B226-marinedrugs-18-00005" ref-type="bibr">226</xref>]</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">Nervous system</td><td align="left" valign="middle" rowspan="1" colspan="1">spirolide C (<bold>210</bold>)/dinoflagellate</td><td align="left" valign="middle" rowspan="1" colspan="1">Polyketide <sup>d</sup>/<break></break>Alkaloid <sup>g</sup></td><td align="left" valign="middle" rowspan="1" colspan="1">nAChR inhibition</td><td align="left" valign="middle" rowspan="1" colspan="1">1.5–3 nM *</td><td align="left" valign="middle" rowspan="1" colspan="1">Muscle and neuronal -type nAChR inhibition</td><td align="left" valign="middle" rowspan="1" colspan="1">FRA</td><td align="left" valign="middle" rowspan="1" colspan="1">[<xref rid="B227-marinedrugs-18-00005" ref-type="bibr">227</xref>]</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">Nervous system</td><td align="left" valign="middle" rowspan="1" colspan="1">zonarol (<bold>211</bold>)/alga</td><td align="left" valign="middle" rowspan="1" colspan="1">Meroterpenoid <sup>f</sup></td><td align="left" valign="middle" rowspan="1" colspan="1">Glutamate toxicity inhibition in vitro</td><td align="left" valign="middle" rowspan="1" colspan="1">0.22 µM</td><td align="left" valign="middle" rowspan="1" colspan="1">Nrf2/ARE pathway activation</td><td align="left" valign="middle" rowspan="1" colspan="1">JPN, USA</td><td align="left" valign="middle" rowspan="1" colspan="1">[<xref rid="B228-marinedrugs-18-00005" ref-type="bibr">228</xref>]</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">Nervous system</td><td align="left" valign="middle" rowspan="1" colspan="1">aplysinellamide-1 (<bold>212</bold>)/sponge</td><td align="left" valign="middle" rowspan="1" colspan="1">Alkaloid <sup>g</sup></td><td align="left" valign="middle" rowspan="1" colspan="1">ApoE secretion modulation</td><td align="left" valign="middle" rowspan="1" colspan="1">30 µM *</td><td align="left" valign="middle" rowspan="1" colspan="1">Undetermined</td><td align="left" valign="middle" rowspan="1" colspan="1">AUS, CAN</td><td align="left" valign="middle" rowspan="1" colspan="1">[<xref rid="B229-marinedrugs-18-00005" ref-type="bibr">229</xref>]</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">Nervous system</td><td align="left" valign="middle" rowspan="1" colspan="1"><italic>A. terreus</italic> lactones (<bold>120</bold>, <bold>121</bold>)/fungus</td><td align="left" valign="middle" rowspan="1" colspan="1">Polyketide <sup>d</sup></td><td align="left" valign="middle" rowspan="1" colspan="1">acetylcholinesterase inhibition</td><td align="left" valign="middle" rowspan="1" colspan="1">4.2 µM</td><td align="left" valign="middle" rowspan="1" colspan="1">Undetermined</td><td align="left" valign="middle" rowspan="1" colspan="1">CHN</td><td align="left" valign="middle" rowspan="1" colspan="1">[<xref rid="B115-marinedrugs-18-00005" ref-type="bibr">115</xref>]</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">Nervous system</td><td align="left" valign="middle" rowspan="1" colspan="1"><italic>C. araneosus</italic> ar3j conotoxin (<bold>213</bold>)/cone snail</td><td align="left" valign="middle" rowspan="1" colspan="1">Peptide <sup>g</sup></td><td align="left" valign="middle" rowspan="1" colspan="1">Sleep induction</td><td align="left" valign="middle" rowspan="1" colspan="1">2 nM *</td><td align="left" valign="middle" rowspan="1" colspan="1">Undetermined</td><td align="left" valign="middle" rowspan="1" colspan="1">IND</td><td align="left" valign="middle" rowspan="1" colspan="1">[<xref rid="B230-marinedrugs-18-00005" ref-type="bibr">230</xref>]</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">Nervous system</td><td align="left" valign="middle" rowspan="1" colspan="1"><italic>D. cejpii</italic> steroid (<bold>214</bold>)/fungus</td><td align="left" valign="middle" rowspan="1" colspan="1">Terpenoid <sup>f</sup></td><td align="left" valign="middle" rowspan="1" colspan="1">Amyloid β-42 production inhibition</td><td align="left" valign="middle" rowspan="1" colspan="1">10 µM *</td><td align="left" valign="middle" rowspan="1" colspan="1">Undetermined</td><td align="left" valign="middle" rowspan="1" colspan="1">DEU, FRA</td><td align="left" valign="middle" rowspan="1" colspan="1">[<xref rid="B231-marinedrugs-18-00005" ref-type="bibr">231</xref>]</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">Nervous system</td><td align="left" valign="middle" rowspan="1" colspan="1">genuanine (<bold>215</bold>)/cone snail</td><td align="left" valign="middle" rowspan="1" colspan="1">Alkaloid <sup>g</sup></td><td align="left" valign="middle" rowspan="1" colspan="1">Paralysis in vivo</td><td align="left" valign="middle" rowspan="1" colspan="1">40 nM *</td><td align="left" valign="middle" rowspan="1" colspan="1">Undetermined</td><td align="left" valign="middle" rowspan="1" colspan="1">PRT, USA</td><td align="left" valign="middle" rowspan="1" colspan="1">[<xref rid="B232-marinedrugs-18-00005" ref-type="bibr">232</xref>] </td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">Nervous system</td><td align="left" valign="middle" rowspan="1" colspan="1">homoaerothionin (<bold>216</bold>)/sponge</td><td align="left" valign="middle" rowspan="1" colspan="1">Alkaloid <sup>g</sup></td><td align="left" valign="middle" rowspan="1" colspan="1">acetylcholinesterase inhibition</td><td align="left" valign="middle" rowspan="1" colspan="1">2.9–6.2 µM </td><td align="left" valign="middle" rowspan="1" colspan="1">Undetermined</td><td align="left" valign="middle" rowspan="1" colspan="1">THA</td><td align="left" valign="middle" rowspan="1" colspan="1">[<xref rid="B233-marinedrugs-18-00005" ref-type="bibr">233</xref>]</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">Nervous system</td><td align="left" valign="middle" rowspan="1" colspan="1">mooreamide A (<bold>217</bold>)/bacterium</td><td align="left" valign="middle" rowspan="1" colspan="1">Polyketide <sup>d</sup></td><td align="left" valign="middle" rowspan="1" colspan="1">CB<sub>1</sub> binding</td><td align="left" valign="middle" rowspan="1" colspan="1">0.47 µM **</td><td align="left" valign="middle" rowspan="1" colspan="1">Undetermined</td><td align="left" valign="middle" rowspan="1" colspan="1">ITA, PNG, USA</td><td align="left" valign="middle" rowspan="1" colspan="1">[<xref rid="B234-marinedrugs-18-00005" ref-type="bibr">234</xref>]</td></tr><tr><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Nervous system</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1"><italic>S. spinosulus</italic> hydroquinone (<bold>218</bold>)/sponge</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Shikimate <sup>h</sup>/Polyketide <sup>d</sup></td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Enhance glutamate and ACh release</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">10 µM *</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Undetermined</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">ITA</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">[<xref rid="B235-marinedrugs-18-00005" ref-type="bibr">235</xref>]</td></tr></tbody></table><table-wrap-foot><fn><p><sup>a</sup><bold>Organism:</bold><italic>Kingdom Animalia</italic>: fish (Phylum Chordata); bryozoan; coral and sea anemone (Phylum Cnidaria); crinoid, sea urchin, starfish (Phylum Echinodermata); cone snail, sea slug (Phylum Mollusca); sponge (Phylum Porifera); <italic>Kingdom Fungi</italic>: fungus; <italic>Kingdom Plantae:</italic> alga; <italic>Kingdom Monera</italic>: bacterium; <italic>Kingdom Protozoa</italic>: dinoflagellates; <sup>b</sup><bold>IC<sub>50</sub></bold>: concentration of a compound required for 50% inhibition, *: apparent IC<sub>50</sub>, **: in vivo study; **: <italic>K</italic><sub>i</sub>: concentration needed to reduce the activity of an enzyme by half; <sup>c</sup><bold>MMOA:</bold> molecular mechanism of action; <sup>d</sup><bold>Country:</bold> AUS: Australia; BEL: Belgium; BRA: Brazil; CAN: Canada; CHN: China; CUB: Cuba; DEU: Germany; DNK: Denmark; EGY: Egypt; ESP: Spain; FIN, Finland; FRA: France; IDN: Indonesia; IND, India; ITA: Italy; JPN: Japan; LKA: Sri Lanka; MEX: Mexico; MYS: Malaysia; NLD: Netherlands; NOR: Norway; PNG: Papua New Guinea; PRT: Portugal; RUS: Russian Federation; S. KOR: South Korea; THA: Thailand; TWN: Taiwan; VNM: Vietnam; <bold>Chemistry:</bold><sup>e</sup> Polyketide; <sup>f</sup> Terpene; <sup>g</sup> Nitrogen-containing compound; <sup>h</sup> Shikimate. <bold>Abbreviations:</bold> Ach: acetylcholine; ApoE: apolipoprotein E; ASIC: acid-sensing sodium ion channel; CAT: catalase; CB<sub>1</sub>: cannabinoid receptor 1; CNS: central nervous system; COX: cyclooxygenase; HO-1: heme oxygenase-1; ICAM: intercellular adhesion molecule-1; IL: interleukin; iNOS: inducible nitric oxide synthase; Kv current: voltage-gated K+ current; MAPK: mitogen-activated protein kinase pathway; MDC/CCL22: macrophage-derived chemokine, C–C motif chemokine 22; nAChR: nicotinic acetylcholine receptor; NA: not available; NF-κB: nuclear factor kappa-light-chain-enhancer of activated B cells; NO: nitric oxide; nAChR: nicotinic acetylcholine receptor; Nrf2-ARE: nuclear transcription factor E2-related factor antioxidant response element; PTP1B: tyrosine protein; phosphatase 1B; ROS: reactive oxygen species; SOD: superoxide dismutase; SOX: superoxide; STAT1: signal transducer and activator of transcription1; TDP-43: trans-activation response DNA-binding protein of 43 kDa.</p></fn></table-wrap-foot></table-wrap><table-wrap id="marinedrugs-18-00005-t003" orientation="portrait" position="float"><object-id pub-id-type="pii">marinedrugs-18-00005-t003_Table 3</object-id><label>Table 3</label><caption><p>Marine pharmacology in 2014–2015: marine compounds with miscellaneous mechanisms of action.</p></caption><table frame="hsides" rules="groups"><thead><tr><th align="left" valign="middle" style="border-top:solid thin;border-bottom:solid thin" rowspan="1" colspan="1">Compound/Organism <sup>a</sup></th><th align="left" valign="middle" style="border-top:solid thin;border-bottom:solid thin" rowspan="1" colspan="1">Chemistry</th><th align="left" valign="middle" style="border-top:solid thin;border-bottom:solid thin" rowspan="1" colspan="1">Pharmacological Activity <sup>i</sup></th><th align="left" valign="middle" style="border-top:solid thin;border-bottom:solid thin" rowspan="1" colspan="1">IC<sub>50</sub><sup>b</sup></th><th align="left" valign="middle" style="border-top:solid thin;border-bottom:solid thin" rowspan="1" colspan="1">MMOA <sup>c</sup></th><th align="left" valign="middle" style="border-top:solid thin;border-bottom:solid thin" rowspan="1" colspan="1">Country <sup>d</sup></th><th align="left" valign="middle" style="border-top:solid thin;border-bottom:solid thin" rowspan="1" colspan="1">References</th></tr></thead><tbody><tr><td align="left" valign="middle" rowspan="1" colspan="1">AdE-1 (<bold>219</bold>)/sea anemone</td><td align="left" valign="middle" rowspan="1" colspan="1">Peptide <sup>g</sup></td><td align="left" valign="middle" rowspan="1" colspan="1">Cardiomyocyte action potential modulation</td><td align="left" valign="middle" rowspan="1" colspan="1">2 nM *</td><td align="left" valign="middle" rowspan="1" colspan="1">Na<sup>+</sup> and K<sup>+</sup> current increase</td><td align="left" valign="middle" rowspan="1" colspan="1">ISR</td><td align="left" valign="middle" rowspan="1" colspan="1">[<xref rid="B236-marinedrugs-18-00005" ref-type="bibr">236</xref>]</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">aaptamine (<bold>220</bold>)/sponge</td><td align="left" valign="middle" rowspan="1" colspan="1">Alkaloid <sup>g</sup></td><td align="left" valign="middle" rowspan="1" colspan="1">ROS inhibition</td><td align="left" valign="middle" rowspan="1" colspan="1">10 μM *</td><td align="left" valign="middle" rowspan="1" colspan="1">Cytokine inhibition</td><td align="left" valign="middle" rowspan="1" colspan="1">S. KOR</td><td align="left" valign="middle" rowspan="1" colspan="1">[<xref rid="B237-marinedrugs-18-00005" ref-type="bibr">237</xref>]</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">amphirionin-4 (<bold>221</bold>)/dinoflagellate</td><td align="left" valign="middle" rowspan="1" colspan="1">Polyketide <sup>e</sup></td><td align="left" valign="middle" rowspan="1" colspan="1">Bone marrow stromal cells proliferation stimulation</td><td align="left" valign="middle" rowspan="1" colspan="1"><0.1 ng/mL</td><td align="left" valign="middle" rowspan="1" colspan="1">Cytoskeleton protein synthesis</td><td align="left" valign="middle" rowspan="1" colspan="1">JPN</td><td align="left" valign="middle" rowspan="1" colspan="1">[<xref rid="B238-marinedrugs-18-00005" ref-type="bibr">238</xref>]</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">astaxanthin (<bold>145</bold>)/alga</td><td align="left" valign="middle" rowspan="1" colspan="1">Terpenoid <sup>f</sup></td><td align="left" valign="middle" rowspan="1" colspan="1">Leydig cell steroidogenesis protection</td><td align="left" valign="middle" rowspan="1" colspan="1">10 µg/mL *</td><td align="left" valign="middle" rowspan="1" colspan="1">ROS scavenging</td><td align="left" valign="middle" rowspan="1" colspan="1">TWN</td><td align="left" valign="middle" rowspan="1" colspan="1">[<xref rid="B239-marinedrugs-18-00005" ref-type="bibr">239</xref>]</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">bastadins 6 and 16 (<bold>222</bold>, <bold>223</bold>)/sponge</td><td align="left" valign="middle" rowspan="1" colspan="1">Alkaloid <sup>g</sup></td><td align="left" valign="middle" rowspan="1" colspan="1">Foam cell formation inhibition </td><td align="left" valign="middle" rowspan="1" colspan="1">5 μM *</td><td align="left" valign="middle" rowspan="1" colspan="1">ACAT inhibition</td><td align="left" valign="middle" rowspan="1" colspan="1">JPN</td><td align="left" valign="middle" rowspan="1" colspan="1">[<xref rid="B240-marinedrugs-18-00005" ref-type="bibr">240</xref>]</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">6,6-bieckol (<bold>224</bold>)/alga</td><td align="left" valign="middle" rowspan="1" colspan="1">Polyketide <sup>e</sup></td><td align="left" valign="middle" rowspan="1" colspan="1">Adipocyte differentiation inhibition</td><td align="left" valign="middle" rowspan="1" colspan="1">50 µg/mL *</td><td align="left" valign="middle" rowspan="1" colspan="1">Adipogenesis inhibition</td><td align="left" valign="middle" rowspan="1" colspan="1">S. KOR</td><td align="left" valign="middle" rowspan="1" colspan="1">[<xref rid="B241-marinedrugs-18-00005" ref-type="bibr">241</xref>]</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">(-)-chlorizidine A (<bold>225</bold>)/bacterium</td><td align="left" valign="middle" rowspan="1" colspan="1">Alkaloid <sup>g</sup></td><td align="left" valign="middle" rowspan="1" colspan="1">Increase G<sub>1</sub> cell cycle phase</td><td align="left" valign="middle" rowspan="1" colspan="1">2 μM *</td><td align="left" valign="middle" rowspan="1" colspan="1">GAPDH and hENO1 binding</td><td align="left" valign="middle" rowspan="1" colspan="1">BRA, USA</td><td align="left" valign="middle" rowspan="1" colspan="1">[<xref rid="B242-marinedrugs-18-00005" ref-type="bibr">242</xref>]</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">dihydroaustrasulfone alcohol (<bold>226</bold>)/soft coral</td><td align="left" valign="middle" rowspan="1" colspan="1">Polyketide <sup>e</sup></td><td align="left" valign="middle" rowspan="1" colspan="1">PDGF-induced HASMC proliferation and angiogenesis inhibition</td><td align="left" valign="middle" rowspan="1" colspan="1">10 μM *</td><td align="left" valign="middle" rowspan="1" colspan="1">DNA synthesis and VEGF signaling inhibition</td><td align="left" valign="middle" rowspan="1" colspan="1">TWN</td><td align="left" valign="middle" rowspan="1" colspan="1">[<xref rid="B243-marinedrugs-18-00005" ref-type="bibr">243</xref>,<xref rid="B244-marinedrugs-18-00005" ref-type="bibr">244</xref>]</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">DPHC (<bold>227</bold>)/alga</td><td align="left" valign="middle" rowspan="1" colspan="1">Terpenoid <sup>f</sup></td><td align="left" valign="middle" rowspan="1" colspan="1">UVB radiation-induced DNA damage protection</td><td align="left" valign="middle" rowspan="1" colspan="1">20 μM *</td><td align="left" valign="middle" rowspan="1" colspan="1">Nucleotide excision repair system induction</td><td align="left" valign="middle" rowspan="1" colspan="1">S. KOR</td><td align="left" valign="middle" rowspan="1" colspan="1">[<xref rid="B245-marinedrugs-18-00005" ref-type="bibr">245</xref>]</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">echinochrome A (<bold>204</bold>)/sea urchin</td><td align="left" valign="middle" rowspan="1" colspan="1">Alkaloid <sup>g</sup></td><td align="left" valign="middle" rowspan="1" colspan="1">Cardiac contractility inhibition</td><td align="left" valign="middle" rowspan="1" colspan="1">3 μM *</td><td align="left" valign="middle" rowspan="1" colspan="1">SERCA2A inhibition</td><td align="left" valign="middle" rowspan="1" colspan="1">BEL, S. KOR, RUS</td><td align="left" valign="middle" rowspan="1" colspan="1">[<xref rid="B246-marinedrugs-18-00005" ref-type="bibr">246</xref>]</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">echinochrome A (<bold>204</bold>)/sea urchin</td><td align="left" valign="middle" rowspan="1" colspan="1">Alkaloid <sup>g</sup></td><td align="left" valign="middle" rowspan="1" colspan="1">Increased mitochondria biogenesis and function</td><td align="left" valign="middle" rowspan="1" colspan="1">5 μM *</td><td align="left" valign="middle" rowspan="1" colspan="1">Mitochondrial biogenesis genes upregulation</td><td align="left" valign="middle" rowspan="1" colspan="1">S. KOR, RUS</td><td align="left" valign="middle" rowspan="1" colspan="1">[<xref rid="B247-marinedrugs-18-00005" ref-type="bibr">247</xref>]</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">eckol (<bold>228</bold>)/alga</td><td align="left" valign="middle" rowspan="1" colspan="1">Polyketide <sup>e</sup></td><td align="left" valign="middle" rowspan="1" colspan="1">ROS suppression in cells</td><td align="left" valign="middle" rowspan="1" colspan="1">10 μM *</td><td align="left" valign="middle" rowspan="1" colspan="1">Increased HO-1 expression</td><td align="left" valign="middle" rowspan="1" colspan="1">S. KOR</td><td align="left" valign="middle" rowspan="1" colspan="1">[<xref rid="B248-marinedrugs-18-00005" ref-type="bibr">248</xref>] </td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">emindole SB (<bold>229</bold>)/fungus</td><td align="left" valign="middle" rowspan="1" colspan="1">Terpenoid <sup>f</sup></td><td align="left" valign="middle" rowspan="1" colspan="1">Nonselective CB<sub>1</sub>/CB<sub>2</sub> antagonist</td><td align="left" valign="middle" rowspan="1" colspan="1">2.2–7.0 μM **</td><td align="left" valign="middle" rowspan="1" colspan="1">Undetermined</td><td align="left" valign="middle" rowspan="1" colspan="1">CHE, DEU</td><td align="left" valign="middle" rowspan="1" colspan="1">[<xref rid="B249-marinedrugs-18-00005" ref-type="bibr">249</xref>]</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">farnesylquinone (<bold>230</bold>)/bacterium</td><td align="left" valign="middle" rowspan="1" colspan="1">Polyketide <sup>e</sup></td><td align="left" valign="middle" rowspan="1" colspan="1">Decreased lipid accumulation </td><td align="left" valign="middle" rowspan="1" colspan="1">1 μM *</td><td align="left" valign="middle" rowspan="1" colspan="1">Increased PPARα activity</td><td align="left" valign="middle" rowspan="1" colspan="1">CHN, DEU </td><td align="left" valign="middle" rowspan="1" colspan="1">[<xref rid="B250-marinedrugs-18-00005" ref-type="bibr">250</xref>]</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">FGFC1 (<bold>231</bold>)/fungus</td><td align="left" valign="middle" rowspan="1" colspan="1">Alkaloid <sup>g</sup></td><td align="left" valign="middle" rowspan="1" colspan="1">Thrombolysis induction in vivo</td><td align="left" valign="middle" rowspan="1" colspan="1">5 mg/kg *</td><td align="left" valign="middle" rowspan="1" colspan="1">Fibrin hydrolysis induction<break></break>in vitro</td><td align="left" valign="middle" rowspan="1" colspan="1">CHN</td><td align="left" valign="middle" rowspan="1" colspan="1">[<xref rid="B251-marinedrugs-18-00005" ref-type="bibr">251</xref>]</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">formosusin A (<bold>232</bold>)/fungus</td><td align="left" valign="middle" rowspan="1" colspan="1">Alkaloid <sup>g</sup></td><td align="left" valign="middle" rowspan="1" colspan="1">Mammalian DNA polymerase β inhibition</td><td align="left" valign="middle" rowspan="1" colspan="1">35.6 μM</td><td align="left" valign="middle" rowspan="1" colspan="1">Competitive and non-competitive inhibition </td><td align="left" valign="middle" rowspan="1" colspan="1">JPN</td><td align="left" valign="middle" rowspan="1" colspan="1">[<xref rid="B252-marinedrugs-18-00005" ref-type="bibr">252</xref>]</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">fucodiphlorethol (<bold>233</bold>)/alga</td><td align="left" valign="middle" rowspan="1" colspan="1">Polyketide <sup>e</sup></td><td align="left" valign="middle" rowspan="1" colspan="1">ROS inhibition</td><td align="left" valign="middle" rowspan="1" colspan="1">10 μM *</td><td align="left" valign="middle" rowspan="1" colspan="1">Decreased mitochondrial loss, and caspase-9 expression</td><td align="left" valign="middle" rowspan="1" colspan="1">S. KOR</td><td align="left" valign="middle" rowspan="1" colspan="1">[<xref rid="B253-marinedrugs-18-00005" ref-type="bibr">253</xref>]</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">gallic acid (<bold>234</bold>)/alga</td><td align="left" valign="middle" rowspan="1" colspan="1">Shikimate <sup>h</sup></td><td align="left" valign="middle" rowspan="1" colspan="1">NO-dependent vasorelaxant effect</td><td align="left" valign="middle" rowspan="1" colspan="1">12.5 µg/mL</td><td align="left" valign="middle" rowspan="1" colspan="1">Phospho-eNOS increase </td><td align="left" valign="middle" rowspan="1" colspan="1">S. KOR</td><td align="left" valign="middle" rowspan="1" colspan="1">[<xref rid="B254-marinedrugs-18-00005" ref-type="bibr">254</xref>]</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">gallinamide A (<bold>235</bold>)/bacterium</td><td align="left" valign="middle" rowspan="1" colspan="1">Peptide <sup>f</sup></td><td align="left" valign="middle" rowspan="1" colspan="1">Human cathepsin L inhibition</td><td align="left" valign="middle" rowspan="1" colspan="1">5 nM</td><td align="left" valign="middle" rowspan="1" colspan="1">Covalent inhibition</td><td align="left" valign="middle" rowspan="1" colspan="1">USA</td><td align="left" valign="middle" rowspan="1" colspan="1">[<xref rid="B255-marinedrugs-18-00005" ref-type="bibr">255</xref>]</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">girolline (<bold>236</bold>)/sponge</td><td align="left" valign="middle" rowspan="1" colspan="1">Alkaloid <sup>g</sup></td><td align="left" valign="middle" rowspan="1" colspan="1">TLR 5 inhibition</td><td align="left" valign="middle" rowspan="1" colspan="1">2 µg/mL</td><td align="left" valign="middle" rowspan="1" colspan="1">IL-8 and IL-6 inhibition</td><td align="left" valign="middle" rowspan="1" colspan="1">CAN, NLD, USA</td><td align="left" valign="middle" rowspan="1" colspan="1">[<xref rid="B256-marinedrugs-18-00005" ref-type="bibr">256</xref>]</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">gracilins A, H, L (<bold>237–239</bold>)/sponge</td><td align="left" valign="middle" rowspan="1" colspan="1">Terpenoid <sup>f</sup></td><td align="left" valign="middle" rowspan="1" colspan="1">mPTP opening inhibition</td><td align="left" valign="middle" rowspan="1" colspan="1">1 μM *</td><td align="left" valign="middle" rowspan="1" colspan="1">Binding to CypD</td><td align="left" valign="middle" rowspan="1" colspan="1">EGY, ESP, GBR</td><td align="left" valign="middle" rowspan="1" colspan="1">[<xref rid="B257-marinedrugs-18-00005" ref-type="bibr">257</xref>]</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1"><italic>H. crispa</italic> polypeptides (<bold>240</bold>, <bold>241</bold>)/sea anemone</td><td align="left" valign="middle" rowspan="1" colspan="1">Peptide <sup>f</sup></td><td align="left" valign="middle" rowspan="1" colspan="1">Macrophage TNF-α, IL-6, and proIL-1β inhibition</td><td align="left" valign="middle" rowspan="1" colspan="1"></td><td align="left" valign="middle" rowspan="1" colspan="1">Trypsin and α-chemotrypsin inhibition</td><td align="left" valign="middle" rowspan="1" colspan="1">RUS, TWN </td><td align="left" valign="middle" rowspan="1" colspan="1">[<xref rid="B258-marinedrugs-18-00005" ref-type="bibr">258</xref>]</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1"><italic>Hyrtios</italic> sp. sesterterpene (<bold>242</bold>)/sponge</td><td align="left" valign="middle" rowspan="1" colspan="1">Terpenoid <sup>f</sup></td><td align="left" valign="middle" rowspan="1" colspan="1">TDP-43 inhibition</td><td align="left" valign="middle" rowspan="1" colspan="1">0.4 nM</td><td align="left" valign="middle" rowspan="1" colspan="1">TDP-43 to DNA binding inhibition</td><td align="left" valign="middle" rowspan="1" colspan="1">ITA, PYF</td><td align="left" valign="middle" rowspan="1" colspan="1">[<xref rid="B259-marinedrugs-18-00005" ref-type="bibr">259</xref>]</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">irciniastatin A (<bold>243</bold>)/sponge</td><td align="left" valign="middle" rowspan="1" colspan="1">Polyketide <sup>e</sup></td><td align="left" valign="middle" rowspan="1" colspan="1">TNF-α receptor 1 ectodomain shedding</td><td align="left" valign="middle" rowspan="1" colspan="1">10 nM *</td><td align="left" valign="middle" rowspan="1" colspan="1">ERK activation induced</td><td align="left" valign="middle" rowspan="1" colspan="1">JPN</td><td align="left" valign="middle" rowspan="1" colspan="1">[<xref rid="B260-marinedrugs-18-00005" ref-type="bibr">260</xref>]</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">iejimalide C (<bold>244</bold>)/ascidian</td><td align="left" valign="middle" rowspan="1" colspan="1">Polyketide <sup>e</sup></td><td align="left" valign="middle" rowspan="1" colspan="1">V-ATPase inhibitor</td><td align="left" valign="middle" rowspan="1" colspan="1">0.12 μM</td><td align="left" valign="middle" rowspan="1" colspan="1">Bafilomycin site binding </td><td align="left" valign="middle" rowspan="1" colspan="1">JPN</td><td align="left" valign="middle" rowspan="1" colspan="1">[<xref rid="B261-marinedrugs-18-00005" ref-type="bibr">261</xref>]</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1"><italic>Laurencia</italic> sp. indole (<bold>245</bold>)/alga</td><td align="left" valign="middle" rowspan="1" colspan="1">Alkaloid <sup>g</sup></td><td align="left" valign="middle" rowspan="1" colspan="1">Aryl hydrocarbon receptor agonist</td><td align="left" valign="middle" rowspan="1" colspan="1">10 μM *</td><td align="left" valign="middle" rowspan="1" colspan="1">DNA binding stimulation and CYP1A1 induction</td><td align="left" valign="middle" rowspan="1" colspan="1">JPN, USA</td><td align="left" valign="middle" rowspan="1" colspan="1">[<xref rid="B262-marinedrugs-18-00005" ref-type="bibr">262</xref>]</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">neopetroside A (<bold>246</bold>)/sponge</td><td align="left" valign="middle" rowspan="1" colspan="1">Alkaloid <sup>g</sup></td><td align="left" valign="middle" rowspan="1" colspan="1">Cardiomyocyte mitochondrial upregulation </td><td align="left" valign="middle" rowspan="1" colspan="1">10 µM *</td><td align="left" valign="middle" rowspan="1" colspan="1">Increased ATP levels and O<sub>2</sub> consumption</td><td align="left" valign="middle" rowspan="1" colspan="1">RUS, S. KOR</td><td align="left" valign="middle" rowspan="1" colspan="1">[<xref rid="B263-marinedrugs-18-00005" ref-type="bibr">263</xref>] </td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">Phlorofucofuroeckol-A (<bold>10</bold>)/alga</td><td align="left" valign="middle" rowspan="1" colspan="1">Polyketide <sup>e</sup></td><td align="left" valign="middle" rowspan="1" colspan="1">Lipid accumulation inhibition</td><td align="left" valign="middle" rowspan="1" colspan="1">18 µM</td><td align="left" valign="middle" rowspan="1" colspan="1">Decreased PPARγ expression</td><td align="left" valign="middle" rowspan="1" colspan="1">S. KOR</td><td align="left" valign="middle" rowspan="1" colspan="1">[<xref rid="B264-marinedrugs-18-00005" ref-type="bibr">264</xref>]</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">polytheonamide B (<bold>247</bold>)/sponge</td><td align="left" valign="middle" rowspan="1" colspan="1">Peptide <sup>g</sup></td><td align="left" valign="middle" rowspan="1" colspan="1">One-ion pore channel permeation determined</td><td align="left" valign="middle" rowspan="1" colspan="1">NA</td><td align="left" valign="middle" rowspan="1" colspan="1">Two ion binding sites defined, but second ion excluded</td><td align="left" valign="middle" rowspan="1" colspan="1">JPN</td><td align="left" valign="middle" rowspan="1" colspan="1">[<xref rid="B265-marinedrugs-18-00005" ref-type="bibr">265</xref>]</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">siphonaxanthin (<bold>248</bold>)/alga</td><td align="left" valign="middle" rowspan="1" colspan="1">Terpenoid <sup>f</sup></td><td align="left" valign="middle" rowspan="1" colspan="1">Adipogenesis inhibition</td><td align="left" valign="middle" rowspan="1" colspan="1">5 µM </td><td align="left" valign="middle" rowspan="1" colspan="1">Transcription factor inhibition</td><td align="left" valign="middle" rowspan="1" colspan="1">JPN</td><td align="left" valign="middle" rowspan="1" colspan="1">[<xref rid="B266-marinedrugs-18-00005" ref-type="bibr">266</xref>]</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">spiromastixones J and L (<bold>57</bold>, <bold>249</bold>)/fungus</td><td align="left" valign="middle" rowspan="1" colspan="1">Polyketide <sup>e</sup></td><td align="left" valign="middle" rowspan="1" colspan="1">Cholesterol uptake inhibition</td><td align="left" valign="middle" rowspan="1" colspan="1">10 μM *</td><td align="left" valign="middle" rowspan="1" colspan="1">PPARγ upregulation</td><td align="left" valign="middle" rowspan="1" colspan="1">CHN</td><td align="left" valign="middle" rowspan="1" colspan="1">[<xref rid="B267-marinedrugs-18-00005" ref-type="bibr">267</xref>]</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">thalassospiramide C (<bold>250</bold>)/bacterium</td><td align="left" valign="middle" rowspan="1" colspan="1">Peptide <sup>g</sup></td><td align="left" valign="middle" rowspan="1" colspan="1">HCAN1 inhibition</td><td align="left" valign="middle" rowspan="1" colspan="1">3.4 nM</td><td align="left" valign="middle" rowspan="1" colspan="1">Binding to Cys115 residue</td><td align="left" valign="middle" rowspan="1" colspan="1">CHN, USA</td><td align="left" valign="middle" rowspan="1" colspan="1">[<xref rid="B268-marinedrugs-18-00005" ref-type="bibr">268</xref>]</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">xyloketal B (<bold>251</bold>)/fungus</td><td align="left" valign="middle" rowspan="1" colspan="1">Polyketide <sup>e</sup></td><td align="left" valign="middle" rowspan="1" colspan="1">Atherosclerotic plaque attenuation</td><td align="left" valign="middle" rowspan="1" colspan="1">14 mg/kg ***</td><td align="left" valign="middle" rowspan="1" colspan="1">Increased eNOS activity</td><td align="left" valign="middle" rowspan="1" colspan="1">CAN, CHN</td><td align="left" valign="middle" rowspan="1" colspan="1">[<xref rid="B269-marinedrugs-18-00005" ref-type="bibr">269</xref>]</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">xyloketal B (<bold>251</bold>)/fungus</td><td align="left" valign="middle" rowspan="1" colspan="1">Polyketide <sup>e</sup></td><td align="left" valign="middle" rowspan="1" colspan="1">P450 3a activity and expression regulation</td><td align="left" valign="middle" rowspan="1" colspan="1">14 mg/kg ***</td><td align="left" valign="middle" rowspan="1" colspan="1">Active site binding determined by docking studies</td><td align="left" valign="middle" rowspan="1" colspan="1">CHN, USA</td><td align="left" valign="middle" rowspan="1" colspan="1">[<xref rid="B270-marinedrugs-18-00005" ref-type="bibr">270</xref>]</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1"><italic>X. testudinaria</italic> lipid (<bold>252</bold>)/sponge</td><td align="left" valign="middle" rowspan="1" colspan="1">Polyketide <sup>e</sup></td><td align="left" valign="middle" rowspan="1" colspan="1">Pancreatic lipase inhibition</td><td align="left" valign="middle" rowspan="1" colspan="1">3.11 μM</td><td align="left" valign="middle" rowspan="1" colspan="1">Triglyceride level decrease in vivo</td><td align="left" valign="middle" rowspan="1" colspan="1">CHN, ITA</td><td align="left" valign="middle" rowspan="1" colspan="1">[<xref rid="B271-marinedrugs-18-00005" ref-type="bibr">271</xref>]</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">acuminolide A (<bold>253</bold>)/dinoflagellate</td><td align="left" valign="middle" rowspan="1" colspan="1">Polyketide <sup>e</sup></td><td align="left" valign="middle" rowspan="1" colspan="1">Stimulation of actomyosin ATPase</td><td align="left" valign="middle" rowspan="1" colspan="1">1 μM *</td><td align="left" valign="middle" rowspan="1" colspan="1">Undetermined</td><td align="left" valign="middle" rowspan="1" colspan="1">S. KOR</td><td align="left" valign="middle" rowspan="1" colspan="1">[<xref rid="B272-marinedrugs-18-00005" ref-type="bibr">272</xref>]</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">ahpatinin Ac (<bold>254</bold>)/bacterium</td><td align="left" valign="middle" rowspan="1" colspan="1">Peptide <sup>g</sup></td><td align="left" valign="middle" rowspan="1" colspan="1">Pepsin inhibition</td><td align="left" valign="middle" rowspan="1" colspan="1">11 nM</td><td align="left" valign="middle" rowspan="1" colspan="1">Undetermined</td><td align="left" valign="middle" rowspan="1" colspan="1">JPN</td><td align="left" valign="middle" rowspan="1" colspan="1">[<xref rid="B273-marinedrugs-18-00005" ref-type="bibr">273</xref>]</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">alternariol derivatives (<bold>255–257</bold>)/sponge</td><td align="left" valign="middle" rowspan="1" colspan="1">Shikimate <sup>h</sup></td><td align="left" valign="middle" rowspan="1" colspan="1">HCV protease inhibition</td><td align="left" valign="middle" rowspan="1" colspan="1">12–52 µg/mL</td><td align="left" valign="middle" rowspan="1" colspan="1">Undetermined</td><td align="left" valign="middle" rowspan="1" colspan="1">EGY, SAU</td><td align="left" valign="middle" rowspan="1" colspan="1">[<xref rid="B136-marinedrugs-18-00005" ref-type="bibr">136</xref>]</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">apliamide D (<bold>258</bold>)/ascidian</td><td align="left" valign="middle" rowspan="1" colspan="1">Peptide <sup>g</sup></td><td align="left" valign="middle" rowspan="1" colspan="1">Na<sup>+</sup>/K<sup>+</sup>-ATPase inhibition</td><td align="left" valign="middle" rowspan="1" colspan="1">3.2 μM</td><td align="left" valign="middle" rowspan="1" colspan="1">Undetermined</td><td align="left" valign="middle" rowspan="1" colspan="1">S. KOR</td><td align="left" valign="middle" rowspan="1" colspan="1">[<xref rid="B274-marinedrugs-18-00005" ref-type="bibr">274</xref>]</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">austalides 4 and 9 (<bold>259</bold>, <bold>260</bold>)/fungus</td><td align="left" valign="middle" rowspan="1" colspan="1">Terpenoid <sup>f</sup></td><td align="left" valign="middle" rowspan="1" colspan="1"><italic>Endo</italic>-1,3-<italic>β</italic>-D-glucanase inhibition</td><td align="left" valign="middle" rowspan="1" colspan="1">0.01 μM</td><td align="left" valign="middle" rowspan="1" colspan="1">Undetermined</td><td align="left" valign="middle" rowspan="1" colspan="1">RUS </td><td align="left" valign="middle" rowspan="1" colspan="1">[<xref rid="B275-marinedrugs-18-00005" ref-type="bibr">275</xref>]</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">axinelline A (<bold>261</bold>)/bacterium</td><td align="left" valign="middle" rowspan="1" colspan="1">Alkaloid <sup>g</sup></td><td align="left" valign="middle" rowspan="1" colspan="1">COX-2 inhibition</td><td align="left" valign="middle" rowspan="1" colspan="1">2.8 μM</td><td align="left" valign="middle" rowspan="1" colspan="1">Undetermined</td><td align="left" valign="middle" rowspan="1" colspan="1">CHN</td><td align="left" valign="middle" rowspan="1" colspan="1">[<xref rid="B276-marinedrugs-18-00005" ref-type="bibr">276</xref>]</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">brevisulcatic acid-4 (<bold>262</bold>)/dinoflagellate</td><td align="left" valign="middle" rowspan="1" colspan="1">Polyketide <sup>e</sup></td><td align="left" valign="middle" rowspan="1" colspan="1">Activation of sodium channels</td><td align="left" valign="middle" rowspan="1" colspan="1">20 ng/mL</td><td align="left" valign="middle" rowspan="1" colspan="1">Undetermined</td><td align="left" valign="middle" rowspan="1" colspan="1">JPN, NZL</td><td align="left" valign="middle" rowspan="1" colspan="1">[<xref rid="B277-marinedrugs-18-00005" ref-type="bibr">277</xref>]</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">4′,5′-dehydrodiodictyonema (<bold>263</bold>)/alga</td><td align="left" valign="middle" rowspan="1" colspan="1">Terpenoid <sup>f</sup></td><td align="left" valign="middle" rowspan="1" colspan="1">PTP1B inhibition</td><td align="left" valign="middle" rowspan="1" colspan="1">2.3 μM</td><td align="left" valign="middle" rowspan="1" colspan="1">Undetermined</td><td align="left" valign="middle" rowspan="1" colspan="1">CHN</td><td align="left" valign="middle" rowspan="1" colspan="1">[<xref rid="B278-marinedrugs-18-00005" ref-type="bibr">278</xref>]</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1"><italic>D. metachromia</italic> sesquiterpenes (<bold>264–266</bold>)/sponge</td><td align="left" valign="middle" rowspan="1" colspan="1">Terpenoid <sup>f</sup></td><td align="left" valign="middle" rowspan="1" colspan="1">Multiple kinases inhibition</td><td align="left" valign="middle" rowspan="1" colspan="1">0.97–4.8 μM</td><td align="left" valign="middle" rowspan="1" colspan="1">Undetermined</td><td align="left" valign="middle" rowspan="1" colspan="1">CHN, NLD, DEU</td><td align="left" valign="middle" rowspan="1" colspan="1">[<xref rid="B279-marinedrugs-18-00005" ref-type="bibr">279</xref>]</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">didemnaketals D and E (<bold>267</bold>, <bold>268</bold>)/ascidian</td><td align="left" valign="middle" rowspan="1" colspan="1">Terpenoid <sup>f</sup></td><td align="left" valign="middle" rowspan="1" colspan="1">Multiple kinases inhibition</td><td align="left" valign="middle" rowspan="1" colspan="1">10 μg/mL *</td><td align="left" valign="middle" rowspan="1" colspan="1">Undetermined</td><td align="left" valign="middle" rowspan="1" colspan="1">EGY</td><td align="left" valign="middle" rowspan="1" colspan="1">[<xref rid="B280-marinedrugs-18-00005" ref-type="bibr">280</xref>]</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">dysiquinol D (<bold>269</bold>)/sponge</td><td align="left" valign="middle" rowspan="1" colspan="1">Terpenoid <sup>f</sup></td><td align="left" valign="middle" rowspan="1" colspan="1">NF-κB inhibition</td><td align="left" valign="middle" rowspan="1" colspan="1">0.81 μM</td><td align="left" valign="middle" rowspan="1" colspan="1">Undetermined</td><td align="left" valign="middle" rowspan="1" colspan="1">AUS, CHN</td><td align="left" valign="middle" rowspan="1" colspan="1">[<xref rid="B281-marinedrugs-18-00005" ref-type="bibr">281</xref>]</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">fucoxanthin (<bold>134</bold>)/alga</td><td align="left" valign="middle" rowspan="1" colspan="1">Terpenoid <sup>f</sup></td><td align="left" valign="middle" rowspan="1" colspan="1">Hydroxyl radical-scavenging</td><td align="left" valign="middle" rowspan="1" colspan="1">10 μg/mL *</td><td align="left" valign="middle" rowspan="1" colspan="1">Undetermined</td><td align="left" valign="middle" rowspan="1" colspan="1">CHN</td><td align="left" valign="middle" rowspan="1" colspan="1">[<xref rid="B282-marinedrugs-18-00005" ref-type="bibr">282</xref>]</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">halenaquinol sulfate (<bold>270</bold>)/sponge</td><td align="left" valign="middle" rowspan="1" colspan="1">Polyketide <sup>e</sup></td><td align="left" valign="middle" rowspan="1" colspan="1">CDK9 and DYRK1A inhibition</td><td align="left" valign="middle" rowspan="1" colspan="1">0.5–0.61 μM</td><td align="left" valign="middle" rowspan="1" colspan="1">Undetermined</td><td align="left" valign="middle" rowspan="1" colspan="1">FRA, NZL</td><td align="left" valign="middle" rowspan="1" colspan="1">[<xref rid="B283-marinedrugs-18-00005" ref-type="bibr">283</xref>]</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">1-hydroxyethylhalenaquinone (<bold>271</bold>)/sponge</td><td align="left" valign="middle" rowspan="1" colspan="1">Polyketide <sup>e</sup></td><td align="left" valign="middle" rowspan="1" colspan="1">Proteasome-chymotrypsin-like activity inhibition</td><td align="left" valign="middle" rowspan="1" colspan="1">0.19 μM</td><td align="left" valign="middle" rowspan="1" colspan="1">Undetermined</td><td align="left" valign="middle" rowspan="1" colspan="1">IDN, JPN, NLD</td><td align="left" valign="middle" rowspan="1" colspan="1">[<xref rid="B284-marinedrugs-18-00005" ref-type="bibr">284</xref>]</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">hymenialdisine derivatives (<bold>272–274</bold>)/sponge</td><td align="left" valign="middle" rowspan="1" colspan="1">Alkaloid <sup>g</sup></td><td align="left" valign="middle" rowspan="1" colspan="1">P<italic>f</italic>GSK-3 inhibition</td><td align="left" valign="middle" rowspan="1" colspan="1">0.07–0.2 μM </td><td align="left" valign="middle" rowspan="1" colspan="1"> Undetermined</td><td align="left" valign="middle" rowspan="1" colspan="1">DEU, EGY, FRA, NLD</td><td align="left" valign="middle" rowspan="1" colspan="1">[<xref rid="B285-marinedrugs-18-00005" ref-type="bibr">285</xref>]</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">hymenialdisine (<bold>275</bold>)/sponge</td><td align="left" valign="middle" rowspan="1" colspan="1">Alkaloid <sup>g</sup></td><td align="left" valign="middle" rowspan="1" colspan="1">CK1, CDK5, GSK3β inhibition</td><td align="left" valign="middle" rowspan="1" colspan="1">0.03–0.16 μM</td><td align="left" valign="middle" rowspan="1" colspan="1"> Undetermined</td><td align="left" valign="middle" rowspan="1" colspan="1">AUS</td><td align="left" valign="middle" rowspan="1" colspan="1">[<xref rid="B286-marinedrugs-18-00005" ref-type="bibr">286</xref>]</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">hyattellactone A (<bold>276</bold>)/sponge</td><td align="left" valign="middle" rowspan="1" colspan="1"> Terpenoid <sup>f</sup></td><td align="left" valign="middle" rowspan="1" colspan="1">PTP1B inhibition</td><td align="left" valign="middle" rowspan="1" colspan="1">7.45 μM</td><td align="left" valign="middle" rowspan="1" colspan="1"> Undetermined</td><td align="left" valign="middle" rowspan="1" colspan="1">IDN, JPN </td><td align="left" valign="middle" rowspan="1" colspan="1">[<xref rid="B287-marinedrugs-18-00005" ref-type="bibr">287</xref>] </td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1"><italic>H. lachne</italic> sesterterpenoid (<bold>277</bold>)/sponge</td><td align="left" valign="middle" rowspan="1" colspan="1"> Terpenoid <sup>f</sup></td><td align="left" valign="middle" rowspan="1" colspan="1">PTP1B inhibition</td><td align="left" valign="middle" rowspan="1" colspan="1">5.2 μM</td><td align="left" valign="middle" rowspan="1" colspan="1"> Undetermined</td><td align="left" valign="middle" rowspan="1" colspan="1">CHN</td><td align="left" valign="middle" rowspan="1" colspan="1">[<xref rid="B288-marinedrugs-18-00005" ref-type="bibr">288</xref>]</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">ianthelliformisamines A–C (<bold>278</bold>, <bold>7</bold>, <bold>8</bold>)/ sponge</td><td align="left" valign="middle" rowspan="1" colspan="1"> Alkaloid <sup>g</sup></td><td align="left" valign="middle" rowspan="1" colspan="1">Carbonic anhydrase inhibition</td><td align="left" valign="middle" rowspan="1" colspan="1">0.2–0.85 μM **</td><td align="left" valign="middle" rowspan="1" colspan="1"> Undetermined</td><td align="left" valign="middle" rowspan="1" colspan="1">AUS, ITA</td><td align="left" valign="middle" rowspan="1" colspan="1">[<xref rid="B289-marinedrugs-18-00005" ref-type="bibr">289</xref>]</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">incisterols A5 and A6 (<bold>279</bold>, <bold>280</bold>)/sponge</td><td align="left" valign="middle" rowspan="1" colspan="1"> Terpenoid <sup>f</sup></td><td align="left" valign="middle" rowspan="1" colspan="1">PXR agonists</td><td align="left" valign="middle" rowspan="1" colspan="1">10 μM *</td><td align="left" valign="middle" rowspan="1" colspan="1"> Undetermined</td><td align="left" valign="middle" rowspan="1" colspan="1">ITA </td><td align="left" valign="middle" rowspan="1" colspan="1">[<xref rid="B290-marinedrugs-18-00005" ref-type="bibr">290</xref>] </td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1"><italic>L. crassum</italic> cembranoid (<bold>281</bold>)/soft coral</td><td align="left" valign="middle" rowspan="1" colspan="1"> Terpenoid <sup>f</sup></td><td align="left" valign="middle" rowspan="1" colspan="1">PPAR transcription activation</td><td align="left" valign="middle" rowspan="1" colspan="1">2.07 μM</td><td align="left" valign="middle" rowspan="1" colspan="1"> Undetermined</td><td align="left" valign="middle" rowspan="1" colspan="1">VNM</td><td align="left" valign="middle" rowspan="1" colspan="1">[<xref rid="B291-marinedrugs-18-00005" ref-type="bibr">291</xref>]</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1"><italic>L. okamurai</italic> terpenoid (<bold>282</bold>)/alga</td><td align="left" valign="middle" rowspan="1" colspan="1">Terpenoid <sup>f</sup></td><td align="left" valign="middle" rowspan="1" colspan="1">PTP1B inhibition</td><td align="left" valign="middle" rowspan="1" colspan="1">4.9 μg/mL</td><td align="left" valign="middle" rowspan="1" colspan="1">Undetermined</td><td align="left" valign="middle" rowspan="1" colspan="1">CHN</td><td align="left" valign="middle" rowspan="1" colspan="1">[<xref rid="B292-marinedrugs-18-00005" ref-type="bibr">292</xref>]</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">malonganenone L (<bold>283</bold>)/sea whip</td><td align="left" valign="middle" rowspan="1" colspan="1">Alkaloid <sup>g</sup></td><td align="left" valign="middle" rowspan="1" colspan="1">PDE4D inhibition</td><td align="left" valign="middle" rowspan="1" colspan="1">8.5 μM</td><td align="left" valign="middle" rowspan="1" colspan="1">Undetermined</td><td align="left" valign="middle" rowspan="1" colspan="1">CHN</td><td align="left" valign="middle" rowspan="1" colspan="1">[<xref rid="B293-marinedrugs-18-00005" ref-type="bibr">293</xref>]</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">punctaporonin K (<bold>284</bold>)/fungus</td><td align="left" valign="middle" rowspan="1" colspan="1">Terpenoid <sup>f</sup></td><td align="left" valign="middle" rowspan="1" colspan="1">Lipid-lowering effect </td><td align="left" valign="middle" rowspan="1" colspan="1">10 μM *</td><td align="left" valign="middle" rowspan="1" colspan="1">Undetermined</td><td align="left" valign="middle" rowspan="1" colspan="1">CHN, DEU</td><td align="left" valign="middle" rowspan="1" colspan="1">[<xref rid="B294-marinedrugs-18-00005" ref-type="bibr">294</xref>]</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">psychrophilin G (<bold>285</bold>)/fungus</td><td align="left" valign="middle" rowspan="1" colspan="1">Peptide <sup>g</sup></td><td align="left" valign="middle" rowspan="1" colspan="1">Lipid-lowering effect</td><td align="left" valign="middle" rowspan="1" colspan="1">10 μM *</td><td align="left" valign="middle" rowspan="1" colspan="1">Undetermined</td><td align="left" valign="middle" rowspan="1" colspan="1">CHN</td><td align="left" valign="middle" rowspan="1" colspan="1">[<xref rid="B295-marinedrugs-18-00005" ref-type="bibr">295</xref>]</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">racemosin (<bold>286</bold>)/alga</td><td align="left" valign="middle" rowspan="1" colspan="1">Alkaloid <sup>g</sup></td><td align="left" valign="middle" rowspan="1" colspan="1">PTP1B inhibition</td><td align="left" valign="middle" rowspan="1" colspan="1">5.9 µM</td><td align="left" valign="middle" rowspan="1" colspan="1">Undetermined</td><td align="left" valign="middle" rowspan="1" colspan="1">CHN</td><td align="left" valign="middle" rowspan="1" colspan="1">[<xref rid="B296-marinedrugs-18-00005" ref-type="bibr">296</xref>]</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">sarcoehrendin B (<bold>287</bold>)/soft coral</td><td align="left" valign="middle" rowspan="1" colspan="1">Polyketide <sup>e</sup></td><td align="left" valign="middle" rowspan="1" colspan="1">PDE4 inhibition</td><td align="left" valign="middle" rowspan="1" colspan="1">3.7 µM</td><td align="left" valign="middle" rowspan="1" colspan="1">Undetermined</td><td align="left" valign="middle" rowspan="1" colspan="1">CHN</td><td align="left" valign="middle" rowspan="1" colspan="1">[<xref rid="B297-marinedrugs-18-00005" ref-type="bibr">297</xref>]</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">sarsolilide A (<bold>288</bold>)/soft coral</td><td align="left" valign="middle" rowspan="1" colspan="1">Terpenoid <sup>f</sup></td><td align="left" valign="middle" rowspan="1" colspan="1">PTP1B inhibition</td><td align="left" valign="middle" rowspan="1" colspan="1">6.8 µM</td><td align="left" valign="middle" rowspan="1" colspan="1">Undetermined</td><td align="left" valign="middle" rowspan="1" colspan="1">CHN, HUN</td><td align="left" valign="middle" rowspan="1" colspan="1">[<xref rid="B298-marinedrugs-18-00005" ref-type="bibr">298</xref>]</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1"><italic>Stachybotry</italic> sp. xanthone (<bold>289</bold>)/fungus</td><td align="left" valign="middle" rowspan="1" colspan="1">Polyketide <sup>e</sup></td><td align="left" valign="middle" rowspan="1" colspan="1">COX-2 inhibition</td><td align="left" valign="middle" rowspan="1" colspan="1">8.9 µM</td><td align="left" valign="middle" rowspan="1" colspan="1">Undetermined</td><td align="left" valign="middle" rowspan="1" colspan="1">CHN</td><td align="left" valign="middle" rowspan="1" colspan="1">[<xref rid="B299-marinedrugs-18-00005" ref-type="bibr">299</xref>]</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1"><italic>S. thunbergii</italic> alkapolyene (<bold>290</bold>)/alga</td><td align="left" valign="middle" rowspan="1" colspan="1">Polyketide <sup>e</sup></td><td align="left" valign="middle" rowspan="1" colspan="1">Soybean LOX inhibition</td><td align="left" valign="middle" rowspan="1" colspan="1">5 µM</td><td align="left" valign="middle" rowspan="1" colspan="1">Undetermined</td><td align="left" valign="middle" rowspan="1" colspan="1">JPN, S. KOR</td><td align="left" valign="middle" rowspan="1" colspan="1">[<xref rid="B300-marinedrugs-18-00005" ref-type="bibr">300</xref>]</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">shinorine (<bold>291</bold>)/alga</td><td align="left" valign="middle" rowspan="1" colspan="1">Alkaloid <sup>g</sup></td><td align="left" valign="middle" rowspan="1" colspan="1"><italic>C. histolyticum</italic> collagenase inhibition</td><td align="left" valign="middle" rowspan="1" colspan="1">104 µM</td><td align="left" valign="middle" rowspan="1" colspan="1">Undetermined</td><td align="left" valign="middle" rowspan="1" colspan="1">AUT</td><td align="left" valign="middle" rowspan="1" colspan="1">[<xref rid="B301-marinedrugs-18-00005" ref-type="bibr">301</xref>]</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">sinularone D (<bold>292</bold>)/soft coral</td><td align="left" valign="middle" rowspan="1" colspan="1">Polyketide <sup>e</sup></td><td align="left" valign="middle" rowspan="1" colspan="1">NF-κB inhibition</td><td align="left" valign="middle" rowspan="1" colspan="1">10 μg/mL *</td><td align="left" valign="middle" rowspan="1" colspan="1">Undetermined</td><td align="left" valign="middle" rowspan="1" colspan="1">CHN</td><td align="left" valign="middle" rowspan="1" colspan="1">[<xref rid="B302-marinedrugs-18-00005" ref-type="bibr">302</xref>]</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1"><italic>N</italic>-(2-benzenepropanoic acid) stachybotrylactam (<bold>293</bold>)/fungus</td><td align="left" valign="middle" rowspan="1" colspan="1">Alkaloid <sup>g</sup></td><td align="left" valign="middle" rowspan="1" colspan="1">Triglyceride and cholesterol inhibition</td><td align="left" valign="middle" rowspan="1" colspan="1">10 μM *</td><td align="left" valign="middle" rowspan="1" colspan="1">Undetermined</td><td align="left" valign="middle" rowspan="1" colspan="1">CHN, DEU </td><td align="left" valign="middle" rowspan="1" colspan="1">[<xref rid="B303-marinedrugs-18-00005" ref-type="bibr">303</xref>]</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">strongylophorine-13/-14 (<bold>294</bold>)/sponge</td><td align="left" valign="middle" rowspan="1" colspan="1">Terpenoid <sup>f</sup></td><td align="left" valign="middle" rowspan="1" colspan="1">Hu proteasome 20S inhibition</td><td align="left" valign="middle" rowspan="1" colspan="1">2.1 μM</td><td align="left" valign="middle" rowspan="1" colspan="1">Undetermined</td><td align="left" valign="middle" rowspan="1" colspan="1">JPN</td><td align="left" valign="middle" rowspan="1" colspan="1">[<xref rid="B304-marinedrugs-18-00005" ref-type="bibr">304</xref>]</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">swinhoeisterol A (<bold>295</bold>)/sponge</td><td align="left" valign="middle" rowspan="1" colspan="1">Terpenoid <sup>f</sup></td><td align="left" valign="middle" rowspan="1" colspan="1">(h)P300 acetyltransferase inhibition</td><td align="left" valign="middle" rowspan="1" colspan="1">2.7 μM</td><td align="left" valign="middle" rowspan="1" colspan="1">Undetermined</td><td align="left" valign="middle" rowspan="1" colspan="1">ITA, CHN, USA</td><td align="left" valign="middle" rowspan="1" colspan="1">[<xref rid="B305-marinedrugs-18-00005" ref-type="bibr">305</xref>]</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">thunberol (<bold>296</bold>)/alga</td><td align="left" valign="middle" rowspan="1" colspan="1">Terpenoid <sup>f</sup></td><td align="left" valign="middle" rowspan="1" colspan="1">PTP1B inhibition</td><td align="left" valign="middle" rowspan="1" colspan="1">2.24 μg/mL</td><td align="left" valign="middle" rowspan="1" colspan="1">Undetermined</td><td align="left" valign="middle" rowspan="1" colspan="1">CHN</td><td align="left" valign="middle" rowspan="1" colspan="1">[<xref rid="B306-marinedrugs-18-00005" ref-type="bibr">306</xref>]</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">xestosaprol O (<bold>297</bold>)/sponge</td><td align="left" valign="middle" rowspan="1" colspan="1">Terpenoid <sup>f</sup></td><td align="left" valign="middle" rowspan="1" colspan="1">IDO1 inhibition</td><td align="left" valign="middle" rowspan="1" colspan="1">4 μM</td><td align="left" valign="middle" rowspan="1" colspan="1">Undetermined</td><td align="left" valign="middle" rowspan="1" colspan="1">CAN, NLD</td><td align="left" valign="middle" rowspan="1" colspan="1">[<xref rid="B307-marinedrugs-18-00005" ref-type="bibr">307</xref>]</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">urupocidin A (<bold>298</bold>)/sponge</td><td align="left" valign="middle" rowspan="1" colspan="1">Alkaloid <sup>g</sup></td><td align="left" valign="middle" rowspan="1" colspan="1">iNOS expression induction</td><td align="left" valign="middle" rowspan="1" colspan="1">10 μM *</td><td align="left" valign="middle" rowspan="1" colspan="1">Undetermined</td><td align="left" valign="middle" rowspan="1" colspan="1">RUS, TWN</td><td align="left" valign="middle" rowspan="1" colspan="1">[<xref rid="B308-marinedrugs-18-00005" ref-type="bibr">308</xref>]</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">variabine B (<bold>299</bold>)/sponge</td><td align="left" valign="middle" rowspan="1" colspan="1">Alkaloid <sup>g</sup></td><td align="left" valign="middle" rowspan="1" colspan="1">Proteasome-chymotrypsin-like activity inhibition</td><td align="left" valign="middle" rowspan="1" colspan="1">4 µg/mL</td><td align="left" valign="middle" rowspan="1" colspan="1">Undetermined</td><td align="left" valign="middle" rowspan="1" colspan="1">IDN, JPN, NLD</td><td align="left" valign="middle" rowspan="1" colspan="1">[<xref rid="B309-marinedrugs-18-00005" ref-type="bibr">309</xref>]</td></tr><tr><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">yoshinone A (<bold>300</bold>)/cyanobacterium</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Polyketide <sup>e</sup></td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Triglyceride inhibition</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">0.4 μM</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Undetermined</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">JPN</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">[<xref rid="B310-marinedrugs-18-00005" ref-type="bibr">310</xref>]</td></tr></tbody></table><table-wrap-foot><fn><p><sup>a</sup><bold>Organism</bold>, <italic>Kingdom Animalia</italic>: ascidian (Phylum Chordata), soft corals, sea whips, and sea anemone (Phylum Cnidaria), dinoflagellates (Phylum Dinoflagellata), sea urchin (Phylum Echinodermata), sponge (Phylum Porifera); <italic>Kingdom Fungi</italic>: fungus; <italic>Kingdom Plantae:</italic> alga; <italic>Kingdom Monera</italic>: bacterium; <sup>b</sup><bold>IC<sub>50</sub></bold>: concentration of a compound required for 50% inhibition in vitro; *: estimated IC<sub>50</sub>; **: Ki; *** in vivo study; <sup>c</sup><bold>MMOA</bold>: molecular mechanism of action; <sup>d</sup><bold>Country:</bold> AUS: Australia; AUT: Austria; BEL: Belgium; BRA: Brazil; CAN: Canada; CHE: Switzerland; CHN: China; DEU: Germany; EGY: Egypt; FRA: France; ESP: Spain; GBR: United Kingdom; HUN: Hungary; IDN: Indonesia; ISR: Israel; ITA: Italy; JPN: Japan; NLD: The Netherlands; NZL: New Zealand; PYF: French Polynesia; RUS: Russian Federation; SAU: Saudi Arabia; S. KOR: South Korea; TWN: Taiwan; VNM: Vietnam; <bold>Chemistry:</bold><sup>e</sup> Polyketide; <sup>f</sup> Terpene; <sup>g</sup> Nitrogen-containing compound; <sup>h</sup> shikimate; <bold>Abbreviations:</bold> ACAT: acyl-CoA:cholesterol acyl-transferase; CB: cannabinoid; CDK: cyclin-dependent kinase; COX-2: cyclooxygenase 2; CK1: casein kinase 1; CypD: cyclophilin D; DDYRK: dual-specificity, tyrosine phosphorylation regulated kinase; DPHC: diphlorethohydroxycarmalol; eNOS: endothelial nitric oxide synthase; ERK: extracellular signal-regulated kinase; GAPDH: D-glyceraldehyde-3-phosphate dehydrogenase; GSK3β: glycogen synthase kinase 3; HASMC: human aortic smooth muscle cells; HCAN1: human calpain 1 protease; HCV: hepatitis C virus; hENO1: human alpha-enolase; hu: human; HO-1: hemeoxygenase-1; IDO1: indoleamine 2, 3 dioxygenase; IL: interleukin; iNOS: inducible nitric oxide synthase; LOX: lipoxygenase; NF-κB: nuclear factor kappa-light-chain-enhancer of activated B cells; NO: nitric oxide; mPTP: mitochondrial permeability transition pore; PDGF: platelet-derived growth factor; PDE4: phosphodiesterase 4; PPAR: peroxisome proliferator-activated receptor; PTP1B: protein tyrosine phosphatase 1B; PXR: pregnane-X-receptor; ROS: reactive oxygen species; SERCA2A: SR Ca<sup>2+</sup> ATPase 2A; TLR5: Toll-like receptor 5; TDP-43: trans-activation response DNA-binding protein of 43 kDa; UVB: ultraviolet B; V-ATPase: vacuolar-type H<sup>+</sup>-ATPase; VEGF: vascular endothelial growth factor.</p></fn></table-wrap-foot></table-wrap></floats-group></pmc></record>Pour manipuler ce document sous Unix (Dilib)
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|texte= Marine Pharmacology in 2014–2015: Marine Compounds with Antibacterial, Antidiabetic, Antifungal, Anti-Inflammatory, Antiprotozoal, Antituberculosis, Antiviral, and Anthelmintic Activities; Affecting the Immune and Nervous Systems, and Other Miscellaneous Mechanisms of Action
}}
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