High Efficiency Drug Repurposing Design for New Antifungal Agents
Identifieur interne : 000698 ( Pmc/Curation ); précédent : 000697; suivant : 000699High Efficiency Drug Repurposing Design for New Antifungal Agents
Auteurs : Jong H. Kim ; Kathleen L. Chan ; Luisa W. Cheng ; Lisa A. Tell ; Barbara A. Byrne ; Kristin Clothier [États-Unis] ; Kirkwood M. LandSource :
- Methods and Protocols [ 2409-9279 ] ; 2019.
Abstract
Current antifungal interventions have often limited efficiency in treating fungal pathogens, particularly those resistant to commercial drugs or fungicides. Antifungal drug repurposing is an alternative intervention strategy, whereby new utility of various marketed, non-antifungal drugs could be repositioned as novel antifungal agents. In this study, we investigated “chemosensitization” as a method to improve the efficiency of antifungal drug repurposing, wherein combined application of a second compound (viz., chemosensitizer) with a conventional, non-antifungal drug could greatly enhance the antifungal activity of the co-applied drug. Redox-active natural compounds or structural derivatives, such as thymol (2-isopropyl-5-methylphenol), 4-isopropyl-3-methylphenol, or 3,5-dimethoxybenzaldehyde, could serve as potent chemosensitizers to enhance antifungal activity of the repurposed drug bithionol. Of note, inclusion of fungal mutants, such as antioxidant mutants, could also facilitate drug repurposing efficiency, which is reflected in the enhancement of antifungal efficacy of bithionol. Bithionol overcame antifungal (viz., fludioxonil) tolerance of the antioxidant mutants of the human/animal pathogen
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DOI: 10.3390/mps2020031
PubMed: 31164611
PubMed Central: 6632159
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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">High Efficiency Drug Repurposing Design for New Antifungal Agents</title><author><name sortKey="Kim, Jong H" sort="Kim, Jong H" uniqKey="Kim J" first="Jong H." last="Kim">Jong H. Kim</name><affiliation><nlm:aff id="af1-mps-02-00031">Foodborne Toxin Detection and Prevention Research Unit, Western Regional Research Center, USDA-ARS, 800 Buchanan St., Albany, CA 94710, USA;<email>kathy.chan@ars.usda.gov</email> (K.L.C.);<email>luisa.cheng@ars.usda.gov</email> (L.W.C.)</nlm:aff></affiliation></author><author><name sortKey="Chan, Kathleen L" sort="Chan, Kathleen L" uniqKey="Chan K" first="Kathleen L." last="Chan">Kathleen L. Chan</name><affiliation><nlm:aff id="af1-mps-02-00031">Foodborne Toxin Detection and Prevention Research Unit, Western Regional Research Center, USDA-ARS, 800 Buchanan St., Albany, CA 94710, USA;<email>kathy.chan@ars.usda.gov</email> (K.L.C.);<email>luisa.cheng@ars.usda.gov</email> (L.W.C.)</nlm:aff></affiliation></author><author><name sortKey="Cheng, Luisa W" sort="Cheng, Luisa W" uniqKey="Cheng L" first="Luisa W." last="Cheng">Luisa W. Cheng</name><affiliation><nlm:aff id="af1-mps-02-00031">Foodborne Toxin Detection and Prevention Research Unit, Western Regional Research Center, USDA-ARS, 800 Buchanan St., Albany, CA 94710, USA;<email>kathy.chan@ars.usda.gov</email> (K.L.C.);<email>luisa.cheng@ars.usda.gov</email> (L.W.C.)</nlm:aff></affiliation></author><author><name sortKey="Tell, Lisa A" sort="Tell, Lisa A" uniqKey="Tell L" first="Lisa A." last="Tell">Lisa A. Tell</name><affiliation><nlm:aff id="af2-mps-02-00031">Department of Medicine and Epidemiology, School of Veterinary Medicine, University of California at Davis, One Shields Avenue, Davis, CA 95616, USA;<email>latell@ucdavis.edu</email></nlm:aff></affiliation></author><author><name sortKey="Byrne, Barbara A" sort="Byrne, Barbara A" uniqKey="Byrne B" first="Barbara A." last="Byrne">Barbara A. Byrne</name><affiliation><nlm:aff id="af3-mps-02-00031">Department of Pathology, Microbiology, and Immunology, School of Veterinary Medicine, University of California at Davis, One Shields Avenue, Davis, CA 95616, USA;<email>bbyrne@ucdavis.edu</email> (B.A.B.);<email>kaclothier@ucdavis.edu</email> (K.C.)</nlm:aff></affiliation></author><author><name sortKey="Clothier, Kristin" sort="Clothier, Kristin" uniqKey="Clothier K" first="Kristin" last="Clothier">Kristin Clothier</name><affiliation><nlm:aff id="af3-mps-02-00031">Department of Pathology, Microbiology, and Immunology, School of Veterinary Medicine, University of California at Davis, One Shields Avenue, Davis, CA 95616, USA;<email>bbyrne@ucdavis.edu</email> (B.A.B.);<email>kaclothier@ucdavis.edu</email> (K.C.)</nlm:aff></affiliation><affiliation wicri:level="1"><nlm:aff id="af4-mps-02-00031">California Animal Health and Food Safety Laboratory, University of California at Davis, One Shields Avenue, Davis, CA 95616, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>California Animal Health and Food Safety Laboratory, University of California at Davis, One Shields Avenue, Davis, CA 95616</wicri:regionArea></affiliation></author><author><name sortKey="Land, Kirkwood M" sort="Land, Kirkwood M" uniqKey="Land K" first="Kirkwood M." last="Land">Kirkwood M. Land</name><affiliation><nlm:aff id="af5-mps-02-00031">Department of Biological Sciences, University of the Pacific, 3601 Pacific Avenue, Stockton, CA 95211, USA;<email>kland@pacific.edu</email></nlm:aff></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">31164611</idno><idno type="pmc">6632159</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6632159</idno><idno type="RBID">PMC:6632159</idno><idno type="doi">10.3390/mps2020031</idno><date when="2019">2019</date><idno type="wicri:Area/Pmc/Corpus">000698</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000698</idno><idno type="wicri:Area/Pmc/Curation">000698</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Curation">000698</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">High Efficiency Drug Repurposing Design for New Antifungal Agents</title><author><name sortKey="Kim, Jong H" sort="Kim, Jong H" uniqKey="Kim J" first="Jong H." last="Kim">Jong H. Kim</name><affiliation><nlm:aff id="af1-mps-02-00031">Foodborne Toxin Detection and Prevention Research Unit, Western Regional Research Center, USDA-ARS, 800 Buchanan St., Albany, CA 94710, USA;<email>kathy.chan@ars.usda.gov</email> (K.L.C.);<email>luisa.cheng@ars.usda.gov</email> (L.W.C.)</nlm:aff></affiliation></author><author><name sortKey="Chan, Kathleen L" sort="Chan, Kathleen L" uniqKey="Chan K" first="Kathleen L." last="Chan">Kathleen L. Chan</name><affiliation><nlm:aff id="af1-mps-02-00031">Foodborne Toxin Detection and Prevention Research Unit, Western Regional Research Center, USDA-ARS, 800 Buchanan St., Albany, CA 94710, USA;<email>kathy.chan@ars.usda.gov</email> (K.L.C.);<email>luisa.cheng@ars.usda.gov</email> (L.W.C.)</nlm:aff></affiliation></author><author><name sortKey="Cheng, Luisa W" sort="Cheng, Luisa W" uniqKey="Cheng L" first="Luisa W." last="Cheng">Luisa W. Cheng</name><affiliation><nlm:aff id="af1-mps-02-00031">Foodborne Toxin Detection and Prevention Research Unit, Western Regional Research Center, USDA-ARS, 800 Buchanan St., Albany, CA 94710, USA;<email>kathy.chan@ars.usda.gov</email> (K.L.C.);<email>luisa.cheng@ars.usda.gov</email> (L.W.C.)</nlm:aff></affiliation></author><author><name sortKey="Tell, Lisa A" sort="Tell, Lisa A" uniqKey="Tell L" first="Lisa A." last="Tell">Lisa A. Tell</name><affiliation><nlm:aff id="af2-mps-02-00031">Department of Medicine and Epidemiology, School of Veterinary Medicine, University of California at Davis, One Shields Avenue, Davis, CA 95616, USA;<email>latell@ucdavis.edu</email></nlm:aff></affiliation></author><author><name sortKey="Byrne, Barbara A" sort="Byrne, Barbara A" uniqKey="Byrne B" first="Barbara A." last="Byrne">Barbara A. Byrne</name><affiliation><nlm:aff id="af3-mps-02-00031">Department of Pathology, Microbiology, and Immunology, School of Veterinary Medicine, University of California at Davis, One Shields Avenue, Davis, CA 95616, USA;<email>bbyrne@ucdavis.edu</email> (B.A.B.);<email>kaclothier@ucdavis.edu</email> (K.C.)</nlm:aff></affiliation></author><author><name sortKey="Clothier, Kristin" sort="Clothier, Kristin" uniqKey="Clothier K" first="Kristin" last="Clothier">Kristin Clothier</name><affiliation><nlm:aff id="af3-mps-02-00031">Department of Pathology, Microbiology, and Immunology, School of Veterinary Medicine, University of California at Davis, One Shields Avenue, Davis, CA 95616, USA;<email>bbyrne@ucdavis.edu</email> (B.A.B.);<email>kaclothier@ucdavis.edu</email> (K.C.)</nlm:aff></affiliation><affiliation wicri:level="1"><nlm:aff id="af4-mps-02-00031">California Animal Health and Food Safety Laboratory, University of California at Davis, One Shields Avenue, Davis, CA 95616, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>California Animal Health and Food Safety Laboratory, University of California at Davis, One Shields Avenue, Davis, CA 95616</wicri:regionArea></affiliation></author><author><name sortKey="Land, Kirkwood M" sort="Land, Kirkwood M" uniqKey="Land K" first="Kirkwood M." last="Land">Kirkwood M. Land</name><affiliation><nlm:aff id="af5-mps-02-00031">Department of Biological Sciences, University of the Pacific, 3601 Pacific Avenue, Stockton, CA 95211, USA;<email>kland@pacific.edu</email></nlm:aff></affiliation></author></analytic><series><title level="j">Methods and Protocols</title><idno type="eISSN">2409-9279</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>Current antifungal interventions have often limited efficiency in treating fungal pathogens, particularly those resistant to commercial drugs or fungicides. Antifungal drug repurposing is an alternative intervention strategy, whereby new utility of various marketed, non-antifungal drugs could be repositioned as novel antifungal agents. In this study, we investigated “chemosensitization” as a method to improve the efficiency of antifungal drug repurposing, wherein combined application of a second compound (viz., chemosensitizer) with a conventional, non-antifungal drug could greatly enhance the antifungal activity of the co-applied drug. Redox-active natural compounds or structural derivatives, such as thymol (2-isopropyl-5-methylphenol), 4-isopropyl-3-methylphenol, or 3,5-dimethoxybenzaldehyde, could serve as potent chemosensitizers to enhance antifungal activity of the repurposed drug bithionol. Of note, inclusion of fungal mutants, such as antioxidant mutants, could also facilitate drug repurposing efficiency, which is reflected in the enhancement of antifungal efficacy of bithionol. Bithionol overcame antifungal (viz., fludioxonil) tolerance of the antioxidant mutants of the human/animal pathogen <italic>Aspergillus fumigatus</italic>. Altogether, our strategy can lead to the development of a high efficiency drug repurposing design, which enhances the susceptibility of pathogens to drugs, reduces time and costs for new antifungal development, and abates drug or fungicide resistance.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Nami, S" uniqKey="Nami S">S. Nami</name></author><author><name sortKey="Aghebati Maleki, A" uniqKey="Aghebati Maleki A">A. Aghebati-Maleki</name></author><author><name sortKey="Morovati, H" uniqKey="Morovati H">H. Morovati</name></author><author><name sortKey="Aghebati Maleki, L" uniqKey="Aghebati Maleki L">L. Aghebati-Maleki</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Nicola, A M" uniqKey="Nicola A">A.M. Nicola</name></author><author><name sortKey="Albuquerque, P" uniqKey="Albuquerque P">P. Albuquerque</name></author><author><name sortKey="Paes, H C" uniqKey="Paes H">H.C. 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<front><journal-meta><journal-id journal-id-type="nlm-ta">Methods Protoc</journal-id><journal-id journal-id-type="iso-abbrev">Methods Protoc</journal-id><journal-id journal-id-type="publisher-id">mps</journal-id><journal-title-group><journal-title>Methods and Protocols</journal-title></journal-title-group><issn pub-type="epub">2409-9279</issn><publisher><publisher-name>MDPI</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">31164611</article-id><article-id pub-id-type="pmc">6632159</article-id><article-id pub-id-type="doi">10.3390/mps2020031</article-id><article-id pub-id-type="publisher-id">mps-02-00031</article-id><article-categories><subj-group subj-group-type="heading"><subject>Communication</subject></subj-group></article-categories><title-group><article-title>High Efficiency Drug Repurposing Design for New Antifungal Agents</article-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Kim</surname><given-names>Jong H.</given-names></name><xref ref-type="aff" rid="af1-mps-02-00031">1</xref><xref rid="c1-mps-02-00031" ref-type="corresp">*</xref></contrib><contrib contrib-type="author"><name><surname>Chan</surname><given-names>Kathleen L.</given-names></name><xref ref-type="aff" rid="af1-mps-02-00031">1</xref></contrib><contrib contrib-type="author"><name><surname>Cheng</surname><given-names>Luisa W.</given-names></name><xref ref-type="aff" rid="af1-mps-02-00031">1</xref></contrib><contrib contrib-type="author"><name><surname>Tell</surname><given-names>Lisa A.</given-names></name><xref ref-type="aff" rid="af2-mps-02-00031">2</xref></contrib><contrib contrib-type="author"><name><surname>Byrne</surname><given-names>Barbara A.</given-names></name><xref ref-type="aff" rid="af3-mps-02-00031">3</xref></contrib><contrib contrib-type="author"><name><surname>Clothier</surname><given-names>Kristin</given-names></name><xref ref-type="aff" rid="af3-mps-02-00031">3</xref><xref ref-type="aff" rid="af4-mps-02-00031">4</xref></contrib><contrib contrib-type="author"><name><surname>Land</surname><given-names>Kirkwood M.</given-names></name><xref ref-type="aff" rid="af5-mps-02-00031">5</xref></contrib></contrib-group><aff id="af1-mps-02-00031"><label>1</label>Foodborne Toxin Detection and Prevention Research Unit, Western Regional Research Center, USDA-ARS, 800 Buchanan St., Albany, CA 94710, USA;<email>kathy.chan@ars.usda.gov</email> (K.L.C.);<email>luisa.cheng@ars.usda.gov</email> (L.W.C.)</aff><aff id="af2-mps-02-00031"><label>2</label>Department of Medicine and Epidemiology, School of Veterinary Medicine, University of California at Davis, One Shields Avenue, Davis, CA 95616, USA;<email>latell@ucdavis.edu</email></aff><aff id="af3-mps-02-00031"><label>3</label>Department of Pathology, Microbiology, and Immunology, School of Veterinary Medicine, University of California at Davis, One Shields Avenue, Davis, CA 95616, USA;<email>bbyrne@ucdavis.edu</email> (B.A.B.);<email>kaclothier@ucdavis.edu</email> (K.C.)</aff><aff id="af4-mps-02-00031"><label>4</label>California Animal Health and Food Safety Laboratory, University of California at Davis, One Shields Avenue, Davis, CA 95616, USA</aff><aff id="af5-mps-02-00031"><label>5</label>Department of Biological Sciences, University of the Pacific, 3601 Pacific Avenue, Stockton, CA 95211, USA;<email>kland@pacific.edu</email></aff><author-notes><corresp id="c1-mps-02-00031"><label>*</label>Correspondence: <email>jongheon.kim@ars.usda.gov</email>; Tel.: +1-510-559-5841</corresp><fn id="fn1-mps-02-00031"><label>†</label><p>This paper is an extended version of our paper published in Kim, J.H.; Chan, K.L.; Cheng, L.W.; Tell, L.A.; Byrne, B.A.; Clothier, K.; Land, K.M. High Efficiency Drug Repurposing for New Antifungal Agents, In Proceedings of 4th International Electronic Conference on Medicinal Chemistry, Basel, Switzerland, 1–30 November 2018.</p></fn></author-notes><pub-date pub-type="epub"><day>17</day><month>4</month><year>2019</year></pub-date><pub-date pub-type="collection"><month>6</month><year>2019</year></pub-date><volume>2</volume><issue>2</issue><elocation-id>31</elocation-id><history><date date-type="received"><day>20</day><month>3</month><year>2019</year></date><date date-type="accepted"><day>12</day><month>4</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>Current antifungal interventions have often limited efficiency in treating fungal pathogens, particularly those resistant to commercial drugs or fungicides. Antifungal drug repurposing is an alternative intervention strategy, whereby new utility of various marketed, non-antifungal drugs could be repositioned as novel antifungal agents. In this study, we investigated “chemosensitization” as a method to improve the efficiency of antifungal drug repurposing, wherein combined application of a second compound (viz., chemosensitizer) with a conventional, non-antifungal drug could greatly enhance the antifungal activity of the co-applied drug. Redox-active natural compounds or structural derivatives, such as thymol (2-isopropyl-5-methylphenol), 4-isopropyl-3-methylphenol, or 3,5-dimethoxybenzaldehyde, could serve as potent chemosensitizers to enhance antifungal activity of the repurposed drug bithionol. Of note, inclusion of fungal mutants, such as antioxidant mutants, could also facilitate drug repurposing efficiency, which is reflected in the enhancement of antifungal efficacy of bithionol. Bithionol overcame antifungal (viz., fludioxonil) tolerance of the antioxidant mutants of the human/animal pathogen <italic>Aspergillus fumigatus</italic>. Altogether, our strategy can lead to the development of a high efficiency drug repurposing design, which enhances the susceptibility of pathogens to drugs, reduces time and costs for new antifungal development, and abates drug or fungicide resistance.</p></abstract><kwd-group><kwd>antifungal intervention</kwd><kwd>antioxidant system</kwd><kwd><italic>Aspergillus</italic></kwd><kwd>chemosensitization</kwd><kwd>drug repurposing</kwd><kwd>drug resistance</kwd><kwd>mutants</kwd><kwd>pathogen control</kwd></kwd-group></article-meta></front><floats-group><fig id="mps-02-00031-f001" orientation="portrait" position="float"><label>Figure 1</label><caption><p>Structures of compounds examined in this study: (<bold>a</bold>) Aspirin; (<bold>b</bold>) bithionol; (<bold>c</bold>) octyl gallate; (<bold>d</bold>) thymol (2-isopropyl-5-methylphenol); (<bold>e</bold>) 4-isopropyl-3-methylphenol; (<bold>f</bold>) 3,5-dimethoxybenzaldehyde.</p></caption><graphic xlink:href="mps-02-00031-g001"></graphic></fig><fig id="mps-02-00031-f002" orientation="portrait" position="float"><label>Figure 2</label><caption><p>Enhancement of antifungal activity of bithionol by thymol tested in <italic>A. fumigatus</italic>. THY, thymol; OG, octyl gallate (positive control).</p></caption><graphic xlink:href="mps-02-00031-g002"></graphic></fig><fig id="mps-02-00031-f003" orientation="portrait" position="float"><label>Figure 3</label><caption><p>Enhancement of antifungal activity of bithionol by 4I3M tested in <italic>A. fumigatus</italic>. 4I3M, 4-isopropyl-3-methylphenol; OG, octyl gallate (positive control).</p></caption><graphic xlink:href="mps-02-00031-g003"></graphic></fig><fig id="mps-02-00031-f004" orientation="portrait" position="float"><label>Figure 4</label><caption><p>Enhancement of antifungal activity of bithionol by thymol or 4I3M tested in the aflatoxigenic <italic>A. parasiticus</italic> 2999. THY, thymol; 4I3M, 4-isopropyl-3-methylphenol; OG, octyl gallate (positive control).</p></caption><graphic xlink:href="mps-02-00031-g004"></graphic></fig><fig id="mps-02-00031-f005" orientation="portrait" position="float"><label>Figure 5</label><caption><p>Enhancement of antifungal activity of bithionol by 3,5-dimethoxybenzaldehyde tested in <italic>A. fumigatus</italic>. 3,5-D, 3,5-dimethoxybenzaldehyde; OG, octyl gallate (positive control).</p></caption><graphic xlink:href="mps-02-00031-g005"></graphic></fig><fig id="mps-02-00031-f006" orientation="portrait" position="float"><label>Figure 6</label><caption><p>Enhancement of the antifungal activity of bithionol by 3,5-dimethoxybenzaldehyde tested in the aflatoxigenic <italic>A. parasiticus</italic> 5862. 3,5-D, 3,5-dimethoxybenzaldehyde; OG, octyl gallate (positive control).</p></caption><graphic xlink:href="mps-02-00031-g006"></graphic></fig><fig id="mps-02-00031-f007" orientation="portrait" position="float"><label>Figure 7</label><caption><p>Scheme of high-efficiency drug repurposing design.</p></caption><graphic xlink:href="mps-02-00031-g007"></graphic></fig><fig id="mps-02-00031-f008" orientation="portrait" position="float"><label>Figure 8</label><caption><p>Bithionol overcomes fludioxonil resistance of <italic>Aspergillus fumigatus</italic> MAPK mutants.</p></caption><graphic xlink:href="mps-02-00031-g008"></graphic></fig><table-wrap id="mps-02-00031-t001" orientation="portrait" position="float"><object-id pub-id-type="pii">mps-02-00031-t001_Table 1</object-id><label>Table 1</label><caption><p>Repositioning of non-antifungal drugs to antifungals.</p></caption><table frame="hsides" rules="groups"><thead><tr><th align="center" valign="top" style="border-top:solid thin;border-bottom:solid thin" rowspan="1" colspan="1">Compounds</th><th align="center" valign="top" style="border-top:solid thin;border-bottom:solid thin" rowspan="1" colspan="1">Functions</th><th align="center" valign="top" style="border-top:solid thin;border-bottom:solid thin" rowspan="1" colspan="1">Repositioning Methods</th><th align="center" valign="top" style="border-top:solid thin;border-bottom:solid thin" rowspan="1" colspan="1">Target Fungi</th><th align="center" valign="top" style="border-top:solid thin;border-bottom:solid thin" rowspan="1" colspan="1">References</th></tr></thead><tbody><tr><td align="center" valign="top" style="border-bottom:solid thin" rowspan="1" colspan="1">Bithionol</td><td align="center" valign="top" style="border-bottom:solid thin" rowspan="1" colspan="1">Anti-parasitic drug</td><td align="center" valign="top" style="border-bottom:solid thin" rowspan="1" colspan="1">High-throughput ATP content assays</td><td align="center" valign="top" style="border-bottom:solid thin" rowspan="1" colspan="1"><italic>Exserohilum rostratum</italic></td><td align="center" valign="top" style="border-bottom:solid thin" rowspan="1" colspan="1">[<xref rid="B39-mps-02-00031" ref-type="bibr">39</xref>]</td></tr><tr><td align="center" valign="top" style="border-bottom:solid thin" rowspan="1" colspan="1">Tacrolimus</td><td align="center" valign="top" style="border-bottom:solid thin" rowspan="1" colspan="1">Immunosuppressive agent</td><td align="center" valign="top" style="border-bottom:solid thin" rowspan="1" colspan="1">The same as above</td><td align="center" valign="top" style="border-bottom:solid thin" rowspan="1" colspan="1"><italic>E. rostratum</italic></td><td align="center" valign="top" style="border-bottom:solid thin" rowspan="1" colspan="1">[<xref rid="B39-mps-02-00031" ref-type="bibr">39</xref>]</td></tr><tr><td align="center" valign="top" style="border-bottom:solid thin" rowspan="1" colspan="1">Floxuridine</td><td align="center" valign="top" style="border-bottom:solid thin" rowspan="1" colspan="1">Antimetabolite</td><td align="center" valign="top" style="border-bottom:solid thin" rowspan="1" colspan="1">The same as above</td><td align="center" valign="top" style="border-bottom:solid thin" rowspan="1" colspan="1"><italic>E. rostratum</italic></td><td align="center" valign="top" style="border-bottom:solid thin" rowspan="1" colspan="1">[<xref rid="B39-mps-02-00031" ref-type="bibr">39</xref>]</td></tr><tr><td align="center" valign="top" style="border-bottom:solid thin" rowspan="1" colspan="1">Auranofin</td><td align="center" valign="top" style="border-bottom:solid thin" rowspan="1" colspan="1">Rheumatoid arthritis drug</td><td align="center" valign="top" style="border-bottom:solid thin" rowspan="1" colspan="1">Clinical & Laboratory Standard Insitute (CLSI) M27-A3 protocol</td><td align="center" valign="top" style="border-bottom:solid thin" rowspan="1" colspan="1"><italic>Candida</italic> and <italic>Cryptococcus</italic> strains</td><td align="center" valign="top" style="border-bottom:solid thin" rowspan="1" colspan="1">[<xref rid="B40-mps-02-00031" ref-type="bibr">40</xref>]</td></tr><tr><td align="center" valign="top" style="border-bottom:solid thin" rowspan="1" colspan="1">Auranofin</td><td align="center" valign="top" style="border-bottom:solid thin" rowspan="1" colspan="1">Rheumatoid arthritis drug</td><td align="center" valign="top" style="border-bottom:solid thin" rowspan="1" colspan="1">CLSI M27-A3 (for yeast) & M38-A2 (for filamentous fungi) protocols</td><td align="center" valign="top" style="border-bottom:solid thin" rowspan="1" colspan="1"><italic>Aspergillus fumigatus</italic>,<break></break><italic>Scedosporium apiospermum</italic>,<break></break><italic>Lomentospora proli</italic><italic>ficans</italic>,<break></break><italic>Candida albicans</italic>,<break></break><italic>Candida krusei</italic>,<break></break><italic>Cryptococcus neoformans</italic></td><td align="center" valign="top" style="border-bottom:solid thin" rowspan="1" colspan="1">[<xref rid="B41-mps-02-00031" ref-type="bibr">41</xref>]</td></tr><tr><td align="center" valign="top" style="border-bottom:solid thin" rowspan="1" colspan="1">Drospirenone</td><td align="center" valign="top" style="border-bottom:solid thin" rowspan="1" colspan="1">Synthetic hormone (birth control pills) w/ethinylestradiol</td><td align="center" valign="top" style="border-bottom:solid thin" rowspan="1" colspan="1">Enhancement of amphotericin B/caspofungin activity against <italic>Candida albicans</italic> biofilms (96-well plate assay)</td><td align="center" valign="top" style="border-bottom:solid thin" rowspan="1" colspan="1"><italic>C. albicans</italic>,<break></break><italic>Candida glabrata</italic></td><td align="center" valign="top" style="border-bottom:solid thin" rowspan="1" colspan="1">[<xref rid="B42-mps-02-00031" ref-type="bibr">42</xref>]</td></tr><tr><td align="center" valign="top" style="border-bottom:solid thin" rowspan="1" colspan="1">Perhexiline</td><td align="center" valign="top" style="border-bottom:solid thin" rowspan="1" colspan="1">Anti-anginal agent</td><td align="center" valign="top" style="border-bottom:solid thin" rowspan="1" colspan="1">The same as above</td><td align="center" valign="top" style="border-bottom:solid thin" rowspan="1" colspan="1">The same as above</td><td align="center" valign="top" style="border-bottom:solid thin" rowspan="1" colspan="1">[<xref rid="B42-mps-02-00031" ref-type="bibr">42</xref>]</td></tr><tr><td align="center" valign="top" style="border-bottom:solid thin" rowspan="1" colspan="1">Toremifine</td><td align="center" valign="top" style="border-bottom:solid thin" rowspan="1" colspan="1">Selective oestrogen receptor modulator (Oestrogen receptor-positive breast cancer treatment)</td><td align="center" valign="top" style="border-bottom:solid thin" rowspan="1" colspan="1">The same as above</td><td align="center" valign="top" style="border-bottom:solid thin" rowspan="1" colspan="1">The same as above</td><td align="center" valign="top" style="border-bottom:solid thin" rowspan="1" colspan="1">[<xref rid="B42-mps-02-00031" ref-type="bibr">42</xref>]</td></tr><tr><td align="center" valign="top" style="border-bottom:solid thin" rowspan="1" colspan="1">Aspirin<break></break>(Acetyl salicylic acid)</td><td align="center" valign="top" style="border-bottom:solid thin" rowspan="1" colspan="1">Anti-pain, fever, or inflammation drug</td><td align="center" valign="top" style="border-bottom:solid thin" rowspan="1" colspan="1">European Committee on Antimicrobial Susceptibility Testing (EUCAST) protocol</td><td align="center" valign="top" style="border-bottom:solid thin" rowspan="1" colspan="1"><italic>C. neoformans</italic>,<break></break><italic>Cryptococcus gatti</italic></td><td align="center" valign="top" style="border-bottom:solid thin" rowspan="1" colspan="1">[<xref rid="B43-mps-02-00031" ref-type="bibr">43</xref>]</td></tr><tr><td align="center" valign="top" style="border-bottom:solid thin" rowspan="1" colspan="1">Ibuprofen</td><td align="center" valign="top" style="border-bottom:solid thin" rowspan="1" colspan="1">Nonsteroidal anti-inflammatory drug</td><td align="center" valign="top" style="border-bottom:solid thin" rowspan="1" colspan="1">The same as above</td><td align="center" valign="top" style="border-bottom:solid thin" rowspan="1" colspan="1">The same as above</td><td align="center" valign="top" style="border-bottom:solid thin" rowspan="1" colspan="1">[<xref rid="B43-mps-02-00031" ref-type="bibr">43</xref>]</td></tr><tr><td align="center" valign="top" style="border-bottom:solid thin" rowspan="1" colspan="1">Human glycogen synthase kinase 3 (GSK-3) inhibitors</td><td align="center" valign="top" style="border-bottom:solid thin" rowspan="1" colspan="1">Neurological disorder drug</td><td align="center" valign="top" style="border-bottom:solid thin" rowspan="1" colspan="1">24-well plate assay</td><td align="center" valign="top" style="border-bottom:solid thin" rowspan="1" colspan="1"><italic>A. fumigatus</italic></td><td align="center" valign="top" style="border-bottom:solid thin" rowspan="1" colspan="1">[<xref rid="B44-mps-02-00031" ref-type="bibr">44</xref>]</td></tr><tr><td align="center" valign="top" style="border-bottom:solid thin" rowspan="1" colspan="1">Octodrine from Johns Hopkins Clinical Compound Library version 1.0.</td><td align="center" valign="top" style="border-bottom:solid thin" rowspan="1" colspan="1">Decongestant drug</td><td align="center" valign="top" style="border-bottom:solid thin" rowspan="1" colspan="1">CLSI M44-A2 protocol</td><td align="center" valign="top" style="border-bottom:solid thin" rowspan="1" colspan="1"><italic>C. albicans</italic></td><td align="center" valign="top" style="border-bottom:solid thin" rowspan="1" colspan="1">[<xref rid="B45-mps-02-00031" ref-type="bibr">45</xref>]</td></tr><tr><td align="center" valign="top" style="border-bottom:solid thin" rowspan="1" colspan="1">Amiodarone from Prestwick library (Off-patent, biologically active molecules)</td><td align="center" valign="top" style="border-bottom:solid thin" rowspan="1" colspan="1">Antiarrhythmic drug</td><td align="center" valign="top" style="border-bottom:solid thin" rowspan="1" colspan="1">High-throughput adenylate kinase assay</td><td align="center" valign="top" style="border-bottom:solid thin" rowspan="1" colspan="1"><italic>C. neoformans</italic></td><td align="center" valign="top" style="border-bottom:solid thin" rowspan="1" colspan="1">[<xref rid="B46-mps-02-00031" ref-type="bibr">46</xref>]</td></tr><tr><td align="center" valign="top" style="border-bottom:solid thin" rowspan="1" colspan="1">Thioridazine</td><td align="center" valign="top" style="border-bottom:solid thin" rowspan="1" colspan="1">Antipsychotic drug</td><td align="center" valign="top" style="border-bottom:solid thin" rowspan="1" colspan="1">The same as above</td><td align="center" valign="top" style="border-bottom:solid thin" rowspan="1" colspan="1"><italic>C. neoformans</italic></td><td align="center" valign="top" style="border-bottom:solid thin" rowspan="1" colspan="1">[<xref rid="B46-mps-02-00031" ref-type="bibr">46</xref>]</td></tr><tr><td align="center" valign="top" style="border-bottom:solid thin" rowspan="1" colspan="1">Artesunate from Pharmakon 1600 repositioning library</td><td align="center" valign="top" style="border-bottom:solid thin" rowspan="1" colspan="1">Antimalarial drug</td><td align="center" valign="top" style="border-bottom:solid thin" rowspan="1" colspan="1">Miconazole synergy test (Anti-biofilm testing)</td><td align="center" valign="top" style="border-bottom:solid thin" rowspan="1" colspan="1"><italic>C. albicans</italic></td><td align="center" valign="top" style="border-bottom:solid thin" rowspan="1" colspan="1">[<xref rid="B47-mps-02-00031" ref-type="bibr">47</xref>]</td></tr><tr><td align="center" valign="top" style="border-bottom:solid thin" rowspan="1" colspan="1">Hexachlorophene</td><td align="center" valign="top" style="border-bottom:solid thin" rowspan="1" colspan="1">Anti-infective (topical) drug</td><td align="center" valign="top" style="border-bottom:solid thin" rowspan="1" colspan="1">The same as above</td><td align="center" valign="top" style="border-bottom:solid thin" rowspan="1" colspan="1"><italic>C. albicans</italic></td><td align="center" valign="top" style="border-bottom:solid thin" rowspan="1" colspan="1">[<xref rid="B47-mps-02-00031" ref-type="bibr">47</xref>]</td></tr><tr><td align="center" valign="top" style="border-bottom:solid thin" rowspan="1" colspan="1">Pyrvinium pamoate</td><td align="center" valign="top" style="border-bottom:solid thin" rowspan="1" colspan="1">Antihelmintic drug</td><td align="center" valign="top" style="border-bottom:solid thin" rowspan="1" colspan="1">The same as above</td><td align="center" valign="top" style="border-bottom:solid thin" rowspan="1" colspan="1"><italic>C. albicans</italic></td><td align="center" valign="top" style="border-bottom:solid thin" rowspan="1" colspan="1">[<xref rid="B47-mps-02-00031" ref-type="bibr">47</xref>]</td></tr><tr><td align="center" valign="top" style="border-bottom:solid thin" rowspan="1" colspan="1">Quinacrine</td><td align="center" valign="top" style="border-bottom:solid thin" rowspan="1" colspan="1">Anti-protozoan drug</td><td align="center" valign="top" style="border-bottom:solid thin" rowspan="1" colspan="1">96-well plate anti-biofilm testing</td><td align="center" valign="top" style="border-bottom:solid thin" rowspan="1" colspan="1"><italic>C. albicans</italic></td><td align="center" valign="top" style="border-bottom:solid thin" rowspan="1" colspan="1">[<xref rid="B48-mps-02-00031" ref-type="bibr">48</xref>]</td></tr><tr><td align="center" valign="top" style="border-bottom:solid thin" rowspan="1" colspan="1">Cyclo-Phosphamide<break></break>(plus 28 drugs)</td><td align="center" valign="top" style="border-bottom:solid thin" rowspan="1" colspan="1">Anti-cancer drug</td><td align="center" valign="top" style="border-bottom:solid thin" rowspan="1" colspan="1">96-well anti-filamentation assay</td><td align="center" valign="top" style="border-bottom:solid thin" rowspan="1" colspan="1"><italic>C. albicans</italic></td><td align="center" valign="top" style="border-bottom:solid thin" rowspan="1" colspan="1">[<xref rid="B49-mps-02-00031" ref-type="bibr">49</xref>]</td></tr><tr><td align="center" valign="top" style="border-bottom:solid thin" rowspan="1" colspan="1">Tosedostat from the Enzo & the Institute for Molecular Medicine Finland oncology collection libraries</td><td align="center" valign="top" style="border-bottom:solid thin" rowspan="1" colspan="1">Anti-cancer (Aminopeptidase inhibitor) drug</td><td align="center" valign="top" style="border-bottom:solid thin" rowspan="1" colspan="1">EUCAST protocol.</td><td align="center" valign="top" style="border-bottom:solid thin" rowspan="1" colspan="1"><italic>C. albicans</italic>,<break></break><italic>C. glabrata</italic></td><td align="center" valign="top" style="border-bottom:solid thin" rowspan="1" colspan="1">[<xref rid="B14-mps-02-00031" ref-type="bibr">14</xref>]</td></tr><tr><td align="center" valign="top" style="border-bottom:solid thin" rowspan="1" colspan="1">Chloroquine</td><td align="center" valign="top" style="border-bottom:solid thin" rowspan="1" colspan="1">Anti-malarial drug</td><td align="center" valign="top" style="border-bottom:solid thin" rowspan="1" colspan="1">Microtiter well plate yeast-to-hyphae transition assay</td><td align="center" valign="top" style="border-bottom:solid thin" rowspan="1" colspan="1"><italic>C. albicans</italic></td><td align="center" valign="top" style="border-bottom:solid thin" rowspan="1" colspan="1">[<xref rid="B50-mps-02-00031" ref-type="bibr">50</xref>]</td></tr><tr><td align="center" valign="top" style="border-bottom:solid thin" rowspan="1" colspan="1">Aliskiren</td><td align="center" valign="top" style="border-bottom:solid thin" rowspan="1" colspan="1">Anti-hypertensive drug</td><td align="center" valign="top" style="border-bottom:solid thin" rowspan="1" colspan="1">CLSI M27-A2 protocol</td><td align="center" valign="top" style="border-bottom:solid thin" rowspan="1" colspan="1"><italic>C. albicans</italic></td><td align="center" valign="top" style="border-bottom:solid thin" rowspan="1" colspan="1">[<xref rid="B51-mps-02-00031" ref-type="bibr">51</xref>]</td></tr><tr><td align="center" valign="top" style="border-bottom:solid thin" rowspan="1" colspan="1">Atorvastatin</td><td align="center" valign="top" style="border-bottom:solid thin" rowspan="1" colspan="1">Anti-hypercholestero-laemia drug</td><td align="center" valign="top" style="border-bottom:solid thin" rowspan="1" colspan="1">CLSI M27-A3 protocol</td><td align="center" valign="top" style="border-bottom:solid thin" rowspan="1" colspan="1"><italic>C. gatti</italic></td><td align="center" valign="top" style="border-bottom:solid thin" rowspan="1" colspan="1">[<xref rid="B52-mps-02-00031" ref-type="bibr">52</xref>]</td></tr><tr><td align="center" valign="top" style="border-bottom:solid thin" rowspan="1" colspan="1">P21-activated protein kinase inhibitor</td><td align="center" valign="top" style="border-bottom:solid thin" rowspan="1" colspan="1">Anti-thyroid cancer drug</td><td align="center" valign="top" style="border-bottom:solid thin" rowspan="1" colspan="1">Agar plate bioassay</td><td align="center" valign="top" style="border-bottom:solid thin" rowspan="1" colspan="1"><italic>Fusarium oxysporum</italic>,<break></break><italic>Fusarium graminearium</italic>,<break></break><italic>Phytopthora</italic> sp.,<break></break><italic>Myrothecium roridum</italic>,<break></break><italic>Helminthosporium maydis.</italic></td><td align="center" valign="top" style="border-bottom:solid thin" rowspan="1" colspan="1">[<xref rid="B53-mps-02-00031" ref-type="bibr">53</xref>]</td></tr></tbody></table></table-wrap></floats-group></pmc></record>Pour manipuler ce document sous Unix (Dilib)
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