3-Bromopyruvate: a novel antifungal agent against the human pathogen Cryptococcus neoformans

Biochem Biophys Res Commun. 2013 May 3;434(2):322-7. doi: 10.1016/j.bbrc.2013.02.125. Epub 2013 Mar 26.

Abstract

We have investigated the antifungal activity of the pyruvic acid analogue: 3-bromopyruvate (3-BP). Growth inhibition by 3-BP of 110 strains of yeast-like and filamentous fungi was tested by standard spot tests or microdilution method. The human pathogen Cryptococcus neoformans exhibited a low Minimal Inhibitory Concentration (MIC) of 0.12-0.15 mM 3-BP. The high toxicity of 3-BP toward C. neoformans correlated with high intracellular accumulation of 3-BP and also with low levels of intracellular ATP and glutathione. Weak cytotoxicity towards mammalian cells and lack of resistance conferred by the PDR (Pleiotropic Drug Resistance) network in the yeast Saccharomyces cerevisiae, are other properties of 3-BP that makes it a novel promising anticryptococcal drug.

Publication types

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

MeSH terms

  • Adenosine Triphosphate / antagonists & inhibitors
  • Adenosine Triphosphate / metabolism
  • Amphotericin B / pharmacology
  • Antifungal Agents / pharmacology*
  • Biological Transport
  • Cryptococcus neoformans / drug effects*
  • Cryptococcus neoformans / pathogenicity
  • Fluconazole / pharmacology
  • Glutathione / metabolism
  • Microbial Sensitivity Tests
  • Microbial Viability / drug effects
  • Pyruvates / pharmacology*
  • Time Factors

Substances

  • Antifungal Agents
  • Pyruvates
  • bromopyruvate
  • Amphotericin B
  • Adenosine Triphosphate
  • Fluconazole
  • Glutathione