High Efficiency Drug Repurposing Design for New Antifungal Agents
| Autor: | Barbara A. Byrne, Lisa A. Tell, Kristin A. Clothier, Kathleen L. Chan, Jong H. Kim, Kirkwood M. Land, Luisa W. Cheng |
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| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Drug media_common.quotation_subject 030106 microbiology Chemosensitizer Antifungal drug Drug resistance Pharmacology Biochemistry Genetics and Molecular Biology (miscellaneous) antifungal intervention Vaccine Related 03 medical and health sciences Structural Biology Chemosensitization Biodefense Medicine lcsh:QH301-705.5 Repurposing media_common mutants pathogen control drug resistance drug repurposing business.industry Prevention Communication chemosensitization Fungicide Drug repositioning Aspergillus 030104 developmental biology Emerging Infectious Diseases Infectious Diseases antioxidant system lcsh:Biology (General) 5.1 Pharmaceuticals Development of treatments and therapeutic interventions business Infection Biotechnology |
| Zdroj: | Methods and Protocols Methods and protocols, vol 2, iss 2 Methods and Protocols, Vol 2, Iss 2, p 31 (2019) |
| ISSN: | 2409-9279 |
| Popis: | 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 Aspergillus fumigatus. 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. |
| Databáze: | OpenAIRE |
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