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

Soumitra Guin; Marhiah C. Montoya; Xiaoyu Wang; Robert Zarnowski; David R. Andes; Marvin J. Meyers; Noelle S. Williams; Damian J. Krysan

doi:10.1101/2024.08.29.610379

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

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

Soumitra Guin, Marhiah C. Montoya, Xiaoyu Wang, Robert Zarnowski, David R. Andes, Marvin J. Meyers, Noelle S. Williams and Damian J. Krysan

bioRxiv

Cold Spring Harbor Laboratory

08/30/2024

DOI: 10.1101/2024.08.29.610379

PMCID: PMC11383691

PMID: 39257751

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https://doi.org/10.1101/2024.08.29.610379View

Preprint (Author's original)This preprint has not been evaluated by subject experts through peer review. Preprints may undergo extensive changes and/or become peer-reviewed journal articles. Open Access

Abstract

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 it penetrates the central nervous system and is active against Candida auris in vivo. These data strongly support the further development of mefloquine analogs as a potentially new class of antifungal molecules.

Details

Title: Subtitle: Analogues of the anti-malaria drug mefloquine have broad spectrum antifungal activity and are efficacious in a model of disseminated Candida auris infection
Creators: Soumitra Guin - Saint Louis University
Marhiah C. Montoya - Duke University
Xiaoyu Wang - The University of Texas Southwestern Medical Center
Robert Zarnowski - University of Wisconsin–Madison
David R. Andes - University of Wisconsin–Madison
Marvin J. Meyers - Saint Louis University
Noelle S. Williams - The University of Texas Southwestern Medical Center
Damian J. Krysan - University of Iowa
Resource Type: Preprint
Publication Details: bioRxiv
DOI: 10.1101/2024.08.29.610379
PMID: 39257751
PMCID: PMC11383691
NLM abbreviation: bioRxiv
eISSN: 2692-8205
Publisher: Cold Spring Harbor Laboratory
Language: English
Date posted: 08/30/2024
Academic Unit: Molecular Physiology and Biophysics; Stead Family Department of Pediatrics; Infectious Disease (Pediatrics)
Record Identifier: 9984702847402771

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