Schizostatin, a novel squalene synthase inhibitor produced by the mushroom, Schizophyllum commune. I. Taxonomy, fermentation, isolation, physico-chemical properties and biological activities

J Antibiot (Tokyo). 1996 Jul;49(7):617-23. doi: 10.7164/antibiotics.49.617.

Abstract

In the process of screening for squalene synthase inhibitors from microbial fermentation products we have isolated a novel compound, named schizostatin (Fig. 1), from the culture broth of the mushroom, Schizophyllum commune SANK 17785. Schizostatin inhibited rat liver microsomal squalene synthase dose dependently and the IC50 value was 0.84 microM. The inhibition was competitive with respect to farnesylpyrophosphate with a Ki value of 0.45 microM.

MeSH terms

  • Alkyl and Aryl Transferases*
  • Animals
  • Anti-Infective Agents / pharmacology
  • Cells, Cultured
  • Cholesterol / biosynthesis
  • Dose-Response Relationship, Drug
  • Enzyme Inhibitors / chemistry*
  • Enzyme Inhibitors / metabolism
  • Enzyme Inhibitors / pharmacology*
  • Farnesyl-Diphosphate Farnesyltransferase / antagonists & inhibitors*
  • Fatty Acids / chemistry*
  • Fatty Acids / metabolism
  • Fatty Acids / pharmacology*
  • Fumarates / chemistry*
  • Fumarates / metabolism
  • Fumarates / pharmacology*
  • Liver / cytology
  • Liver / drug effects
  • Liver / metabolism
  • Male
  • Mice
  • Mice, Inbred Strains
  • Microbial Sensitivity Tests
  • Rats
  • Rats, Wistar
  • Schizophyllum / chemistry
  • Schizophyllum / metabolism*
  • Schizophyllum / physiology
  • Transferases / antagonists & inhibitors

Substances

  • Anti-Infective Agents
  • Enzyme Inhibitors
  • Fatty Acids
  • Fumarates
  • schizostatin
  • Cholesterol
  • Transferases
  • Alkyl and Aryl Transferases
  • p21(ras) farnesyl-protein transferase
  • Farnesyl-Diphosphate Farnesyltransferase