title: Stresgenin B, an inhibitor of heat-induced heat shock protein gene expression, produced by Streptomyces sp. AS-9.
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.
authors.affiliation: Department of Bioactive Molecules, National Institute of Infectious Diseases, Tokyo, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Akagawa
authors.forename: Y
authors.initials: Y
authors.lastname: Takano
authors.forename: A
authors.initials: A
authors.lastname: Ishii
authors.forename: S
authors.initials: S
authors.lastname: Mizuno
authors.forename: R
authors.initials: R
authors.lastname: Izui
authors.forename: T
authors.initials: T
authors.lastname: Sameshima
authors.forename: N
authors.initials: N
authors.lastname: Kawamura
authors.forename: K
authors.initials: K
authors.lastname: Dobashi
authors.forename: T
authors.initials: T
authors.lastname: Yoshioka
mesh_terms: D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D001833:Body Temperature Regulation / Q000187:drug effects; D016466:CHO Cells; D006224:Cricetinae; D004149:Dioxoles / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D015870:Gene Expression / Q000187:drug effects; D006360:Heat-Shock Proteins / Q000235:genetics*; D006358:Hot Temperature; D006801:Humans; D051379:Mice; D013302:Streptomyces / Q000145:classification* / Q000378:metabolism
chemical_list: D000903:Antibiotics, Antineoplastic; D004149:Dioxoles; D006360:Heat-Shock Proteins; C403865:stresgenin B