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Cited by 71Antifungal resistance and susceptibilityFungal Plant Pathogen ControlMicrobial Natural Products and Biosynthesis

Antifungal Drug Repurposing

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Kim, Jong H., Cheng, Luisa W., Chan, Kathleen L., Tam, Christina C., Mahoney, Noreen, Friedman, Mendel, Shilman, Mikhail Martchenko, Land, Kirkwood M.·2020·Antibiotics
DOI 10.3390/antibiotics9110812PMC PMC7697925
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Abstract

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 Aspergillus fumigatus having TR34/L98H mutations, specifically, a 34 bp insertion into the cytochrome P450 51A (CYP51A) gene promoter region and a leucine-to-histidine substitution at codon 98 of CYP51A. 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.

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Cited by

Sorted by citations

Authors
Kim, J. H., Cheng, L. W., Chan, K. L., Tam, C. C., Mahoney, N., Friedman, M., Shilman, M. M., & Land, K. M.
Affiliations
  • Agricultural Research Service (US)
  • Keck Graduate Institute (US)
  • University of the Pacific (US)
Corresponding author
Kim, Jong H.
ORCID
Venue
Antibiotics
Publisher
MDPI AG
Published
2020-11-15
Volume
9
Issue
11
Pages
812
ISSN
2079-6382 (ISSN-L)
DOI
10.3390/antibiotics9110812
PMC
PMC7697925
OpenAlex
W3099475559
Cited by
71
References
15
Citations by year
2026: 6 · 2025: 13 · 2024: 15 · 2023: 12 · 2022: 15 · 2021: 10
FWCI
1.21
Type
journal article
Language
en
Open access
Licence
Locations
  • Antibiotics (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Scholarly Commons (University of the Pacific) (submittedVersion, cc-by)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
Agricultural Research Service (USDA-ARS CRIS Project 5325-42000-039-00D)
Topics
  • Health Sciences › Medicine › Infectious Diseases › Antifungal resistance and susceptibility
  • Life Sciences › Agricultural and Biological Sciences › Ecology, Evolution, Behavior and Systematics › Fungal Plant Pathogen Control
  • Health Sciences › Medicine › Pharmacology › Microbial Natural Products and Biosynthesis
Keywords
antifungal drug repurposing, antifungal resistance, azole resistance, echinocandin resistance, cyp51A mutations, TR34/L98H mutation, Aspergillus fumigatus, azole fungicides, antifungal drug discovery, fungal pathogens

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