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

Antimicrob Agents Chemother. 2024 Nov 6;68(11):e0130124. doi: 10.1128/aac.01301-24. Epub 2024 Oct 4.

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 that 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.

Keywords: Candida auris; antifungal agents; antifungal therapy.

MeSH terms

  • Animals
  • Antifungal Agents* / pharmacology
  • Antifungal Agents* / therapeutic use
  • Antimalarials* / pharmacology
  • Antimalarials* / therapeutic use
  • Candida / drug effects
  • Candida auris / drug effects
  • Candidiasis / drug therapy
  • Candidiasis / microbiology
  • Candidiasis, Invasive
  • Humans
  • Mefloquine* / pharmacology
  • Mefloquine* / therapeutic use
  • Mice
  • Microbial Sensitivity Tests*

Substances

  • Antifungal Agents
  • Mefloquine
  • Antimalarials

Supplementary concepts

  • Candida auris infection