Bisabosquals, novel squalene synthase inhibitors. I. Taxonomy, fermentation, isolation and biological activities

J Antibiot (Tokyo). 2001 Nov;54(11):890-5. doi: 10.7164/antibiotics.54.890.

Abstract

In the course of screening for yeast squalene synthase inhibitors, bisabosqual A was isolated from the culture broth of Stachybotrys sp. RF-7260. The related compounds bisabosquals B, C and D were also isolated from Stachybotrys ruwenzoriensis RF-6853. Bisabosquals inhibited squalene synthases. IC50 values of bisabosqual A against the microsomal squalene synthases from Saccharomyces cerevisiae, Candida albicans, HepG2 cell and rat liver were 0.43, 0.25, 0.95 and 2.5 microg/ml, respectively. Bisabosqual C exhibited inhibitory activities similar to bisabosqual A. Bisabosqual A showed broad spectrum antifungal activity in vitro.

MeSH terms

  • Animals
  • Antifungal Agents / isolation & purification*
  • Antifungal Agents / pharmacology
  • Enzyme Inhibitors / isolation & purification*
  • Enzyme Inhibitors / pharmacology
  • Farnesyl-Diphosphate Farnesyltransferase / antagonists & inhibitors*
  • Fermentation
  • Hepatocytes
  • Humans
  • Inhibitory Concentration 50
  • Microbial Sensitivity Tests
  • Pyrans / isolation & purification*
  • Pyrans / pharmacology
  • Rats
  • Stachybotrys / chemistry
  • Stachybotrys / classification
  • Stachybotrys / metabolism*

Substances

  • Antifungal Agents
  • Enzyme Inhibitors
  • Pyrans
  • Farnesyl-Diphosphate Farnesyltransferase