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

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