Analogs of the anti-malaria drug mefloquine have broad-spectrum antifungal activity and are efficacious in a model of disseminated Candida auris infection

Only three classes of antifungal drugs are currently in clinical use. Here, we report that derivatives of the malarial drug mefloquine have broad-spectrum antifungal activity including difficult-to-treat molds and endemic fungi. Pharmacokinetic and efficacy studies of NSC-4377 indicate that it penet...

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Bibliographic Details
Published in:Antimicrobial agents and chemotherapy 2024-11, Vol.68 (11), p.e0130124
Main Authors: Guin, Soumitra, Montoya, Marhiah C, Wang, Xiaoyu, Zarnowski, Robert, Andes, David R, Meyers, Marvin J, Williams, Noelle S, Krysan, Damian J
Format: Article
Language:English
Subjects:
Animals
Antifungal Agents - pharmacology
Antifungal Agents - therapeutic use
Antimalarials - pharmacology
Antimalarials - therapeutic use
Antimicrobial Chemotherapy
Candida - drug effects
Candida auris - drug effects
Candidiasis - drug therapy
Candidiasis - microbiology
Candidiasis, Invasive
Experimental Therapeutics
Humans
Mefloquine - pharmacology
Mefloquine - therapeutic use
Mice
Microbial Sensitivity Tests
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Summary:Only three classes of antifungal drugs are currently in clinical use. Here, we report that derivatives of the malarial drug mefloquine have broad-spectrum antifungal activity including difficult-to-treat molds and endemic fungi. Pharmacokinetic and efficacy studies of NSC-4377 indicate that it penetrates the central nervous system and is active against . These data strongly support the further development of mefloquine analogs as a potentially new class of antifungal molecules.
ISSN:0066-4804
1098-6596
1098-6596
DOI:10.1128/aac.01301-24