Distorted Gold(I)-Phosphine Complexes as Antifungal Agents

J Med Chem. 2020 Mar 12;63(5):2455-2469. doi: 10.1021/acs.jmedchem.9b01436. Epub 2019 Dec 16.

Abstract

Fungi cause serious nosocomial infections including candidiasis and aspergillosis, some of which display reduced susceptibility to current antifungals. Inorganic compounds have been found to be beneficial against various medical ailments but have yet to be applied to fungal infections. Here, we explore the activity of linear and square-planar gold(I)-phosphine complexes against a panel of 28 fungal strains including Candida spp., Cryptococcus spp., Aspergillus spp., and Fusarium spp. Notably, two square-planar gold(I) complexes with excellent broad-spectrum activity display potent antifungal effects against strains of Candida auris, an emerging multidrug-resistant fungus that presents a serious global health threat. To characterize the biological activity of these gold(I) complexes, we used a series of time-kill studies, cytotoxicity and hemolysis assays, as well as whole-cell uptake and development of resistance studies.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Antifungal Agents / chemistry
  • Antifungal Agents / pharmacology*
  • Coordination Complexes / chemistry
  • Coordination Complexes / pharmacology*
  • Fungi / drug effects*
  • Gold / chemistry
  • Gold / pharmacology*
  • Humans
  • Microbial Sensitivity Tests
  • Models, Molecular
  • Mycoses / drug therapy
  • Phosphines / chemistry
  • Phosphines / pharmacology*

Substances

  • Antifungal Agents
  • Coordination Complexes
  • Phosphines
  • Gold
  • phosphine