Antifungal Drug Repurposing
Control of fungal pathogens is increasingly problematic due to the limited number of effective drugs available for antifungal therapy. Conventional antifungal drugs could also trigger human cytotoxicity associated with the kidneys and liver, including the generation of reactive oxygen species. Moreo...
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2020-11-01
|
| Series: | Antibiotics |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2079-6382/9/11/812 |
| _version_ | 1797547847285997568 |
|---|---|
| author | Jong H. Kim Luisa W. Cheng Kathleen L. Chan Christina C. Tam Noreen Mahoney Mendel Friedman Mikhail Martchenko Shilman Kirkwood M. Land |
| author_facet | Jong H. Kim Luisa W. Cheng Kathleen L. Chan Christina C. Tam Noreen Mahoney Mendel Friedman Mikhail Martchenko Shilman Kirkwood M. Land |
| author_sort | Jong H. Kim |
| collection | DOAJ |
| description | Control of fungal pathogens is increasingly problematic due to the limited number of effective drugs available for antifungal therapy. Conventional antifungal drugs could also trigger human cytotoxicity associated with the kidneys and liver, including the generation of reactive oxygen species. Moreover, increased incidences of fungal resistance to the classes of azoles, such as fluconazole, itraconazole, voriconazole, or posaconazole, or echinocandins, including caspofungin, anidulafungin, or micafungin, have been documented. Of note, certain azole fungicides such as propiconazole or tebuconazole that are applied to agricultural fields have the same mechanism of antifungal action as clinical azole drugs. Such long-term application of azole fungicides to crop fields provides environmental selection pressure for the emergence of pan-azole-resistant fungal strains such as <i>Aspergillus fumigatus</i> having TR34/L98H mutations, specifically, a 34 bp insertion into the cytochrome P450 51A (<i>CYP51A</i>) gene promoter region and a leucine-to-histidine substitution at codon 98 of <i>CYP51A</i>. Altogether, the emerging resistance of pathogens to currently available antifungal drugs and insufficiency in the discovery of new therapeutics engender the urgent need for the development of new antifungals and/or alternative therapies for effective control of fungal pathogens. We discuss the current needs for the discovery of new clinical antifungal drugs and the recent drug repurposing endeavors as alternative methods for fungal pathogen control. |
| first_indexed | 2024-03-10T14:50:03Z |
| format | Article |
| id | doaj.art-b562247ee26b4c6f9f7797d5848b2d4f |
| institution | Directory Open Access Journal |
| issn | 2079-6382 |
| language | English |
| last_indexed | 2024-03-10T14:50:03Z |
| publishDate | 2020-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Antibiotics |
| spelling | doaj.art-b562247ee26b4c6f9f7797d5848b2d4f2023-11-20T21:02:50ZengMDPI AGAntibiotics2079-63822020-11-0191181210.3390/antibiotics9110812Antifungal Drug RepurposingJong H. Kim0Luisa W. Cheng1Kathleen L. Chan2Christina C. Tam3Noreen Mahoney4Mendel Friedman5Mikhail Martchenko Shilman6Kirkwood M. Land7Foodborne Toxin Detection and Prevention Research Unit, Western Regional Research Center, Agricultural Research Service, United States Department of Agriculture, Albany, CA 94710, USAFoodborne Toxin Detection and Prevention Research Unit, Western Regional Research Center, Agricultural Research Service, United States Department of Agriculture, Albany, CA 94710, USAFoodborne Toxin Detection and Prevention Research Unit, Western Regional Research Center, Agricultural Research Service, United States Department of Agriculture, Albany, CA 94710, USAFoodborne Toxin Detection and Prevention Research Unit, Western Regional Research Center, Agricultural Research Service, United States Department of Agriculture, Albany, CA 94710, USAFoodborne Toxin Detection and Prevention Research Unit, Western Regional Research Center, Agricultural Research Service, United States Department of Agriculture, Albany, CA 94710, USAHealthy Processed Foods Research Unit, Western Regional Research Center, Agricultural Research Service, United States Department of Agriculture, Albany, CA 94710, USAHenry E. Riggs School of Applied Life Sciences, Keck Graduate Institute, Claremont, CA 91711, USADepartment of Biological Sciences, University of the Pacific, Stockton, CA 95211, USAControl of fungal pathogens is increasingly problematic due to the limited number of effective drugs available for antifungal therapy. Conventional antifungal drugs could also trigger human cytotoxicity associated with the kidneys and liver, including the generation of reactive oxygen species. Moreover, increased incidences of fungal resistance to the classes of azoles, such as fluconazole, itraconazole, voriconazole, or posaconazole, or echinocandins, including caspofungin, anidulafungin, or micafungin, have been documented. Of note, certain azole fungicides such as propiconazole or tebuconazole that are applied to agricultural fields have the same mechanism of antifungal action as clinical azole drugs. Such long-term application of azole fungicides to crop fields provides environmental selection pressure for the emergence of pan-azole-resistant fungal strains such as <i>Aspergillus fumigatus</i> having TR34/L98H mutations, specifically, a 34 bp insertion into the cytochrome P450 51A (<i>CYP51A</i>) gene promoter region and a leucine-to-histidine substitution at codon 98 of <i>CYP51A</i>. Altogether, the emerging resistance of pathogens to currently available antifungal drugs and insufficiency in the discovery of new therapeutics engender the urgent need for the development of new antifungals and/or alternative therapies for effective control of fungal pathogens. We discuss the current needs for the discovery of new clinical antifungal drugs and the recent drug repurposing endeavors as alternative methods for fungal pathogen control.https://www.mdpi.com/2079-6382/9/11/812antifungal<i>Aspergillus</i><i>Candida</i><i>Cryptococcus</i>drug repurposingmultidrug resistance |
| spellingShingle | Jong H. Kim Luisa W. Cheng Kathleen L. Chan Christina C. Tam Noreen Mahoney Mendel Friedman Mikhail Martchenko Shilman Kirkwood M. Land Antifungal Drug Repurposing Antibiotics antifungal <i>Aspergillus</i> <i>Candida</i> <i>Cryptococcus</i> drug repurposing multidrug resistance |
| title | Antifungal Drug Repurposing |
| title_full | Antifungal Drug Repurposing |
| title_fullStr | Antifungal Drug Repurposing |
| title_full_unstemmed | Antifungal Drug Repurposing |
| title_short | Antifungal Drug Repurposing |
| title_sort | antifungal drug repurposing |
| topic | antifungal <i>Aspergillus</i> <i>Candida</i> <i>Cryptococcus</i> drug repurposing multidrug resistance |
| url | https://www.mdpi.com/2079-6382/9/11/812 |
| work_keys_str_mv | AT jonghkim antifungaldrugrepurposing AT luisawcheng antifungaldrugrepurposing AT kathleenlchan antifungaldrugrepurposing AT christinactam antifungaldrugrepurposing AT noreenmahoney antifungaldrugrepurposing AT mendelfriedman antifungaldrugrepurposing AT mikhailmartchenkoshilman antifungaldrugrepurposing AT kirkwoodmland antifungaldrugrepurposing |