Bisabosquals, novel squalene synthase inhibitors. I. Taxonomy, fermentation, isolation and biological activities.
In the course of screening for yeast squalene synthase inhibitors, bisabosqual A was isolated from the culture broth of Stachybotrys sp. RF-7260. The related compounds bisabosquals B, C and D were also isolated from Stachybotrys ruwenzoriensis RF-6853. Bisabosquals inhibited squalene synthases. IC50 values of bisabosqual A against the microsomal squalene synthases from Saccharomyces cerevisiae, Candida albicans, HepG2 cell and rat liver were 0.43, 0.25, 0.95 and 2.5 microg/ml, respectively. Bisabosqual C exhibited inhibitory activities similar to bisabosqual A. Bisabosqual A showed broad spectrum antifungal activity in vitro.
Minagawa
K
K
Shionogi Research Laboratories, Shionogi & Co., Ltd., Osaka, Japan. kazuyuki.minagawa@shionogi.co.jp
Kouzuki
S
S
Nomura
K
K
Yamaguchi
T
T
Kawamura
Y
Y
Matsushima
K
K
Tani
H
H
Ishii
K
K
Tanimoto
T
T
Kamigauchi
T
T
D000818:Animals; D000935:Antifungal Agents / Q000302:isolation & purification* / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000302:isolation & purification* / Q000494:pharmacology; D013186:Farnesyl-Diphosphate Farnesyltransferase / Q000037:antagonists & inhibitors*; D005285:Fermentation; D022781:Hepatocytes; D006801:Humans; D020128:Inhibitory Concentration 50; D008826:Microbial Sensitivity Tests; D011714:Pyrans / Q000302:isolation & purification* / Q000494:pharmacology; D051381:Rats; D013191:Stachybotrys / Q000737:chemistry / Q000145:classification / Q000378:metabolism*
D000935:Antifungal Agents; D004791:Enzyme Inhibitors; D011714:Pyrans; D013186:Farnesyl-Diphosphate Farnesyltransferase