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Novel Peroxides as Promising Anticancer Agents with Unexpected Depressed Antimalarial Activity.

Identifieur interne : 000096 ( PubMed/Checkpoint ); précédent : 000095; suivant : 000097

Novel Peroxides as Promising Anticancer Agents with Unexpected Depressed Antimalarial Activity.

Auteurs : Paolo Coghi [République populaire de Chine] ; Ivan A. Yaremenko [Russie] ; Parichat Prommana [Thaïlande] ; Peter S. Radulov [Russie] ; Mikhail A. Syroeshkin [Russie] ; Yu Jun Wu [République populaire de Chine] ; Jia Ying Gao [République populaire de Chine] ; Floria M. Gordillo [République populaire de Chine] ; Simon Mok [République populaire de Chine] ; Vincent Kam Wai Wong [République populaire de Chine] ; Chairat Uthaipibull [Thaïlande] ; Alexander O. Terent'Ev [Russie]

Source :

RBID : pubmed:29469179

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English descriptors

Abstract

Twenty six peroxides belonging to bridged 1,2,4,5-tetraoxanes, bridged 1,2,4-trioxolanes (ozonides), and tricyclic monoperoxides were evaluated for their in vitro antimalarial activity against Plasmodium falciparum (3D7) and for their cytotoxic activities against immortalized human normal fibroblast (CCD19Lu), liver (LO2 ), and lung (BEAS-2B) cell lines as well as human liver (HepG2) and lung (A549) cancer-cell lines. Synthetic ozonides were shown to have the highest cytotoxicity on HepG2 (IC50 =0.19-0.59 μm), and some of these compounds selectively targeted liver cancer (selectivity index values for compounds 13 a and 14 a are 20 and 28, respectively) at levels that, in some cases, were higher than those of paclitaxel, artemisinin, and artesunic acid. In contrast some ozonides showed only moderate antimalarial activity against the chloroquine-sensitive 3D7 strain of P. falciparum (IC50 from 2.76 to 24.2 μm; 12 b, IC50 =2.76 μm; 13 a, IC50 =20.14 μm; 14 a, IC50 =6.32 μm). These results suggest that these derivatives have divergent mechanisms of action against cancer cells and malaria-infected cells. A cyclic voltammetry study of the peroxides was performed, but most of the compounds did not show direct correlation in oxidative capacity-activity. Our findings offer a new source of antimalarial and anticancer agents through structural modification of peroxide compounds.

DOI: 10.1002/cmdc.201700804
PubMed: 29469179


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pubmed:29469179

Le document en format XML

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<div type="abstract" xml:lang="en">Twenty six peroxides belonging to bridged 1,2,4,5-tetraoxanes, bridged 1,2,4-trioxolanes (ozonides), and tricyclic monoperoxides were evaluated for their in vitro antimalarial activity against Plasmodium falciparum (3D7) and for their cytotoxic activities against immortalized human normal fibroblast (CCD19Lu), liver (LO
<sub>2</sub>
), and lung (BEAS-2B) cell lines as well as human liver (HepG2) and lung (A549) cancer-cell lines. Synthetic ozonides were shown to have the highest cytotoxicity on HepG2 (IC
<sub>50</sub>
=0.19-0.59 μm), and some of these compounds selectively targeted liver cancer (selectivity index values for compounds 13 a and 14 a are 20 and 28, respectively) at levels that, in some cases, were higher than those of paclitaxel, artemisinin, and artesunic acid. In contrast some ozonides showed only moderate antimalarial activity against the chloroquine-sensitive 3D7 strain of P. falciparum (IC
<sub>50</sub>
from 2.76 to 24.2 μm; 12 b, IC
<sub>50</sub>
=2.76 μm; 13 a, IC
<sub>50</sub>
=20.14 μm; 14 a, IC
<sub>50</sub>
=6.32 μm). These results suggest that these derivatives have divergent mechanisms of action against cancer cells and malaria-infected cells. A cyclic voltammetry study of the peroxides was performed, but most of the compounds did not show direct correlation in oxidative capacity-activity. Our findings offer a new source of antimalarial and anticancer agents through structural modification of peroxide compounds.</div>
</front>
</TEI>
<pubmed>
<MedlineCitation Status="MEDLINE" Owner="NLM">
<PMID Version="1">29469179</PMID>
<DateCompleted>
<Year>2019</Year>
<Month>04</Month>
<Day>24</Day>
</DateCompleted>
<DateRevised>
<Year>2019</Year>
<Month>04</Month>
<Day>24</Day>
</DateRevised>
<Article PubModel="Print-Electronic">
<Journal>
<ISSN IssnType="Electronic">1860-7187</ISSN>
<JournalIssue CitedMedium="Internet">
<Volume>13</Volume>
<Issue>9</Issue>
<PubDate>
<Year>2018</Year>
<Month>05</Month>
<Day>08</Day>
</PubDate>
</JournalIssue>
<Title>ChemMedChem</Title>
<ISOAbbreviation>ChemMedChem</ISOAbbreviation>
</Journal>
<ArticleTitle>Novel Peroxides as Promising Anticancer Agents with Unexpected Depressed Antimalarial Activity.</ArticleTitle>
<Pagination>
<MedlinePgn>902-908</MedlinePgn>
</Pagination>
<ELocationID EIdType="doi" ValidYN="Y">10.1002/cmdc.201700804</ELocationID>
<Abstract>
<AbstractText>Twenty six peroxides belonging to bridged 1,2,4,5-tetraoxanes, bridged 1,2,4-trioxolanes (ozonides), and tricyclic monoperoxides were evaluated for their in vitro antimalarial activity against Plasmodium falciparum (3D7) and for their cytotoxic activities against immortalized human normal fibroblast (CCD19Lu), liver (LO
<sub>2</sub>
), and lung (BEAS-2B) cell lines as well as human liver (HepG2) and lung (A549) cancer-cell lines. Synthetic ozonides were shown to have the highest cytotoxicity on HepG2 (IC
<sub>50</sub>
=0.19-0.59 μm), and some of these compounds selectively targeted liver cancer (selectivity index values for compounds 13 a and 14 a are 20 and 28, respectively) at levels that, in some cases, were higher than those of paclitaxel, artemisinin, and artesunic acid. In contrast some ozonides showed only moderate antimalarial activity against the chloroquine-sensitive 3D7 strain of P. falciparum (IC
<sub>50</sub>
from 2.76 to 24.2 μm; 12 b, IC
<sub>50</sub>
=2.76 μm; 13 a, IC
<sub>50</sub>
=20.14 μm; 14 a, IC
<sub>50</sub>
=6.32 μm). These results suggest that these derivatives have divergent mechanisms of action against cancer cells and malaria-infected cells. A cyclic voltammetry study of the peroxides was performed, but most of the compounds did not show direct correlation in oxidative capacity-activity. Our findings offer a new source of antimalarial and anticancer agents through structural modification of peroxide compounds.</AbstractText>
<CopyrightInformation>© 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.</CopyrightInformation>
</Abstract>
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<Author ValidYN="Y">
<LastName>Coghi</LastName>
<ForeName>Paolo</ForeName>
<Initials>P</Initials>
<AffiliationInfo>
<Affiliation>State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Avenida Wai Long, Taipa, Macau, China.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y">
<LastName>Yaremenko</LastName>
<ForeName>Ivan A</ForeName>
<Initials>IA</Initials>
<AffiliationInfo>
<Affiliation>N.D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, Leninsky Prospect 47, Moscow, 119991, Russian Federation.</Affiliation>
</AffiliationInfo>
<AffiliationInfo>
<Affiliation>Faculty of Chemical and Pharmaceutical Technology and Biomedical Products, D.I. Mendeleev University of Chemical Technology of Russia, 9 Miusskaya Square, Moscow, 125047, Russia.</Affiliation>
</AffiliationInfo>
<AffiliationInfo>
<Affiliation>All Russian Research Institute for Phytopathology, 143050 B. Vyazyomy, Moscow Region, Russia.</Affiliation>
</AffiliationInfo>
</Author>
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<LastName>Prommana</LastName>
<ForeName>Parichat</ForeName>
<Initials>P</Initials>
<AffiliationInfo>
<Affiliation>National Center for Genetic Engineering and Biotechnology (BIOTEC), National Science and Technology Development Agency (NSTDA), 113 Thailand Science Park, Pathum Thani, 12120, Thailand.</Affiliation>
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<LastName>Radulov</LastName>
<ForeName>Peter S</ForeName>
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<Affiliation>N.D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, Leninsky Prospect 47, Moscow, 119991, Russian Federation.</Affiliation>
</AffiliationInfo>
<AffiliationInfo>
<Affiliation>All Russian Research Institute for Phytopathology, 143050 B. Vyazyomy, Moscow Region, Russia.</Affiliation>
</AffiliationInfo>
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<LastName>Syroeshkin</LastName>
<ForeName>Mikhail A</ForeName>
<Initials>MA</Initials>
<AffiliationInfo>
<Affiliation>N.D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, Leninsky Prospect 47, Moscow, 119991, Russian Federation.</Affiliation>
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<LastName>Gao</LastName>
<ForeName>Jia Ying</ForeName>
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<ForeName>Floria M</ForeName>
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</AffiliationInfo>
</Author>
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<LastName>Mok</LastName>
<ForeName>Simon</ForeName>
<Initials>S</Initials>
<AffiliationInfo>
<Affiliation>State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Avenida Wai Long, Taipa, Macau, China.</Affiliation>
</AffiliationInfo>
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<Author ValidYN="Y">
<LastName>Wong</LastName>
<ForeName>Vincent Kam Wai</ForeName>
<Initials>VKW</Initials>
<AffiliationInfo>
<Affiliation>State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Avenida Wai Long, Taipa, Macau, China.</Affiliation>
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<LastName>Uthaipibull</LastName>
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<Affiliation>National Center for Genetic Engineering and Biotechnology (BIOTEC), National Science and Technology Development Agency (NSTDA), 113 Thailand Science Park, Pathum Thani, 12120, Thailand.</Affiliation>
</AffiliationInfo>
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<Author ValidYN="Y">
<LastName>Terent'ev</LastName>
<ForeName>Alexander O</ForeName>
<Initials>AO</Initials>
<AffiliationInfo>
<Affiliation>N.D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, Leninsky Prospect 47, Moscow, 119991, Russian Federation.</Affiliation>
</AffiliationInfo>
<AffiliationInfo>
<Affiliation>Faculty of Chemical and Pharmaceutical Technology and Biomedical Products, D.I. Mendeleev University of Chemical Technology of Russia, 9 Miusskaya Square, Moscow, 125047, Russia.</Affiliation>
</AffiliationInfo>
<AffiliationInfo>
<Affiliation>All Russian Research Institute for Phytopathology, 143050 B. Vyazyomy, Moscow Region, Russia.</Affiliation>
</AffiliationInfo>
</Author>
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<Language>eng</Language>
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<PublicationType UI="D016428">Journal Article</PublicationType>
<PublicationType UI="D013485">Research Support, Non-U.S. Gov't</PublicationType>
</PublicationTypeList>
<ArticleDate DateType="Electronic">
<Year>2018</Year>
<Month>03</Month>
<Day>15</Day>
</ArticleDate>
</Article>
<MedlineJournalInfo>
<Country>Germany</Country>
<MedlineTA>ChemMedChem</MedlineTA>
<NlmUniqueID>101259013</NlmUniqueID>
<ISSNLinking>1860-7179</ISSNLinking>
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<ChemicalList>
<Chemical>
<RegistryNumber>0</RegistryNumber>
<NameOfSubstance UI="D000962">Antimalarials</NameOfSubstance>
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<Chemical>
<RegistryNumber>0</RegistryNumber>
<NameOfSubstance UI="D000970">Antineoplastic Agents</NameOfSubstance>
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<RegistryNumber>0</RegistryNumber>
<NameOfSubstance UI="D010545">Peroxides</NameOfSubstance>
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<CitationSubset>IM</CitationSubset>
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<CommentsCorrections RefType="ErratumIn">
<RefSource>ChemMedChem. 2018 Oct 22;13(20):2249</RefSource>
<PMID Version="1">30350346</PMID>
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<MeshHeadingList>
<MeshHeading>
<DescriptorName UI="D000072283" MajorTopicYN="N">A549 Cells</DescriptorName>
</MeshHeading>
<MeshHeading>
<DescriptorName UI="D000962" MajorTopicYN="N">Antimalarials</DescriptorName>
<QualifierName UI="Q000138" MajorTopicYN="N">chemical synthesis</QualifierName>
<QualifierName UI="Q000737" MajorTopicYN="N">chemistry</QualifierName>
<QualifierName UI="Q000494" MajorTopicYN="Y">pharmacology</QualifierName>
</MeshHeading>
<MeshHeading>
<DescriptorName UI="D000970" MajorTopicYN="N">Antineoplastic Agents</DescriptorName>
<QualifierName UI="Q000138" MajorTopicYN="N">chemical synthesis</QualifierName>
<QualifierName UI="Q000737" MajorTopicYN="N">chemistry</QualifierName>
<QualifierName UI="Q000494" MajorTopicYN="Y">pharmacology</QualifierName>
</MeshHeading>
<MeshHeading>
<DescriptorName UI="D045744" MajorTopicYN="N">Cell Line, Tumor</DescriptorName>
</MeshHeading>
<MeshHeading>
<DescriptorName UI="D049109" MajorTopicYN="N">Cell Proliferation</DescriptorName>
<QualifierName UI="Q000187" MajorTopicYN="N">drug effects</QualifierName>
</MeshHeading>
<MeshHeading>
<DescriptorName UI="D002470" MajorTopicYN="N">Cell Survival</DescriptorName>
<QualifierName UI="Q000187" MajorTopicYN="N">drug effects</QualifierName>
</MeshHeading>
<MeshHeading>
<DescriptorName UI="D004305" MajorTopicYN="N">Dose-Response Relationship, Drug</DescriptorName>
</MeshHeading>
<MeshHeading>
<DescriptorName UI="D004354" MajorTopicYN="N">Drug Screening Assays, Antitumor</DescriptorName>
</MeshHeading>
<MeshHeading>
<DescriptorName UI="D056945" MajorTopicYN="N">Hep G2 Cells</DescriptorName>
</MeshHeading>
<MeshHeading>
<DescriptorName UI="D006801" MajorTopicYN="N">Humans</DescriptorName>
</MeshHeading>
<MeshHeading>
<DescriptorName UI="D008288" MajorTopicYN="N">Malaria</DescriptorName>
<QualifierName UI="Q000188" MajorTopicYN="Y">drug therapy</QualifierName>
</MeshHeading>
<MeshHeading>
<DescriptorName UI="D015394" MajorTopicYN="N">Molecular Structure</DescriptorName>
</MeshHeading>
<MeshHeading>
<DescriptorName UI="D021261" MajorTopicYN="N">Parasitic Sensitivity Tests</DescriptorName>
</MeshHeading>
<MeshHeading>
<DescriptorName UI="D010545" MajorTopicYN="N">Peroxides</DescriptorName>
<QualifierName UI="Q000138" MajorTopicYN="N">chemical synthesis</QualifierName>
<QualifierName UI="Q000737" MajorTopicYN="N">chemistry</QualifierName>
<QualifierName UI="Q000494" MajorTopicYN="Y">pharmacology</QualifierName>
</MeshHeading>
<MeshHeading>
<DescriptorName UI="D010963" MajorTopicYN="N">Plasmodium falciparum</DescriptorName>
<QualifierName UI="Q000187" MajorTopicYN="Y">drug effects</QualifierName>
<QualifierName UI="Q000254" MajorTopicYN="N">growth & development</QualifierName>
</MeshHeading>
<MeshHeading>
<DescriptorName UI="D013329" MajorTopicYN="N">Structure-Activity Relationship</DescriptorName>
</MeshHeading>
</MeshHeadingList>
<KeywordList Owner="NOTNLM">
<Keyword MajorTopicYN="Y">cancer</Keyword>
<Keyword MajorTopicYN="Y">cytotoxicity</Keyword>
<Keyword MajorTopicYN="Y">malaria</Keyword>
<Keyword MajorTopicYN="Y">ozonides</Keyword>
<Keyword MajorTopicYN="Y">peroxides</Keyword>
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<Year>2017</Year>
<Month>12</Month>
<Day>19</Day>
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<Year>2018</Year>
<Month>02</Month>
<Day>15</Day>
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