Stresgenin B, an inhibitor of heat-induced heat shock protein gene expression, produced by Streptomyces sp. AS-9

J Antibiot (Tokyo). 1999 Nov;52(11):960-70. doi: 10.7164/antibiotics.52.960.

Abstract

Stresgenin B was isolated as an inhibitor of heat-induced heat shock protein (HSP) gene expression from a culture broth of Streptomyces sp. AS-9 by silica gel chromatography and HPLC. The molecular formula of the novel compound was determined as C11H13NO5 by high resolution FAB-MS analysis, and the structure was determined by UV, 1H NMR, 13C NMR, HMQC, HMBC, and NOESY spectra. Stresgenin B inhibited heat-induced luciferase reporter-gene expression directed by the human hsp70B promoter in Chinese hamster ovary (CHO) cells at concentrations lower than the concentrations for inhibition of dexamethasone-induced luciferase reporter-gene expression directed by the mouse mammary tumor virus (MMTV)-LTR promoter. The inhibition of heat-induced reporter gene expression was evident even when cells were exposed to stresgenin B only during heat stress treatment. Moreover, the compound inhibited heat-induced syntheses of hsp72/73, hsp90, and hsp110 and thereby suppressed the induction of thermotolerance. Stresgenin B showed moderate cytotoxic activities against several neoplastic cell lines and also showed antibacterial activities against Micrococcus luteus, Bacillus subtilis and Staphylococcus aureus strains.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibiotics, Antineoplastic / chemistry
  • Antibiotics, Antineoplastic / isolation & purification*
  • Antibiotics, Antineoplastic / pharmacology
  • Body Temperature Regulation / drug effects
  • CHO Cells
  • Cricetinae
  • Dioxoles / chemistry
  • Dioxoles / isolation & purification*
  • Dioxoles / pharmacology
  • Gene Expression / drug effects
  • Heat-Shock Proteins / genetics*
  • Hot Temperature
  • Humans
  • Mice
  • Streptomyces / classification*
  • Streptomyces / metabolism

Substances

  • Antibiotics, Antineoplastic
  • Dioxoles
  • Heat-Shock Proteins
  • stresgenin B