High Efficiency Drug Repurposing Design for New Antifungal Agents
Identifieur interne : 000242 ( an2020/Analysis ); précédent : 000241; suivant : 000243High 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
Url:
DOI: 10.3390/mps2020031
PubMed: 31164611
PubMed Central: 6632159
Affiliations:
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PMC:6632159Le document en format XML
<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><wicri:noRegion>CA 95616</wicri:noRegion></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><idno type="wicri:Area/Pmc/Checkpoint">000722</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Checkpoint">000722</idno><idno type="wicri:Area/Ncbi/Merge">000673</idno><idno type="wicri:Area/Ncbi/Curation">000673</idno><idno type="wicri:Area/Ncbi/Checkpoint">000673</idno><idno type="wicri:Area/Main/Merge">000780</idno><idno type="wicri:Area/Main/Curation">000780</idno><idno type="wicri:Area/Main/Exploration">000780</idno><idno type="wicri:Area/an2020/Extraction">000242</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><wicri:noRegion>CA 95616</wicri:noRegion></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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Chan</name><name sortKey="Cheng, Luisa W" sort="Cheng, Luisa W" uniqKey="Cheng L" first="Luisa W." last="Cheng">Luisa W. Cheng</name><name sortKey="Kim, Jong H" sort="Kim, Jong H" uniqKey="Kim J" first="Jong H." last="Kim">Jong H. Kim</name><name sortKey="Land, Kirkwood M" sort="Land, Kirkwood M" uniqKey="Land K" first="Kirkwood M." last="Land">Kirkwood M. Land</name><name sortKey="Tell, Lisa A" sort="Tell, Lisa A" uniqKey="Tell L" first="Lisa A." last="Tell">Lisa A. Tell</name></noCountry><country name="États-Unis"><noRegion><name sortKey="Clothier, Kristin" sort="Clothier, Kristin" uniqKey="Clothier K" first="Kristin" last="Clothier">Kristin Clothier</name></noRegion></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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