Broad-Spectrum Antifungal Agents: Fluorinated Aryl- and Heteroaryl-Substituted Hydrazones

ChemMedChem. 2021 Jan 8;16(1):124-133. doi: 10.1002/cmdc.202000626. Epub 2020 Oct 16.

Abstract

Fluorinated aryl- and heteroaryl-substituted monohydrazones displayed excellent broad-spectrum activity against various fungal strains, including a panel of clinically relevant Candida auris strains relative to a control antifungal agent, voriconazole (VRC). These monohydrazones displayed less hemolysis of murine red blood cells than that of VRC at the same concentrations, possessed fungicidal activity in a time-kill study, and exhibited no mammalian cell cytotoxicity. In addition, these monohydrazones prevented the formation of biofilms that otherwise block antibiotic effectiveness and did not trigger the development of resistance when exposed to C. auris AR Bank # 0390 over 15 passages.

Keywords: Biofilm; Candida auris; Cytotoxicity; Drug resistance; Hemolysis; Monohydrazones.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antifungal Agents / chemical synthesis
  • Antifungal Agents / chemistry*
  • Antifungal Agents / pharmacology
  • Biofilms / drug effects
  • Candida / drug effects
  • Candida / physiology
  • Cell Line
  • Cell Survival / drug effects
  • Drug Resistance, Microbial / drug effects
  • Halogenation
  • Hemolysis / drug effects
  • Humans
  • Hydrazones / chemical synthesis
  • Hydrazones / chemistry*
  • Hydrazones / pharmacology
  • Mice
  • Microbial Sensitivity Tests
  • Structure-Activity Relationship
  • Voriconazole / pharmacology

Substances

  • Antifungal Agents
  • Hydrazones
  • Voriconazole