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 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.
Akagawa
H
H
Department of Bioactive Molecules, National Institute of Infectious Diseases, Tokyo, Japan.
Takano
Y
Y
Ishii
A
A
Mizuno
S
S
Izui
R
R
Sameshima
T
T
Kawamura
N
N
Dobashi
K
K
Yoshioka
T
T
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
D000903:Antibiotics, Antineoplastic; D004149:Dioxoles; D006360:Heat-Shock Proteins; C403865:stresgenin B