CJ-15,183, a new inhibitor of squalene synthase produced by a fungus, Aspergillus aculeatus.
A new squalene synthase (SSase) inhibitor, CJ-15,183 (I) was isolated from the fermentation broth of a fungus, Aspergillus aculeatus CL38916. The compound potently inhibited rat liver and Candida albicans microsomal SSases and also inhibited the human enzyme. It also showed antifungal activities against filamentous fungi and a yeast. The structure was determined to be an aliphatic tetracarboxylic acid compound consisting of an alkyl gamma-lactone, malic acid and isocitric acid moieties by spectroscopic studies.
Watanabe
S
S
Exploratory Medicinal Sciences, PGRD, Nagoya Laboratories, Pfizer Pharmaceuticals Inc., Aichi, Japan. shuzo.watanabe@japan.pfizer.com
Hirai
H
H
Ishiguro
M
M
Kambara
T
T
Kojima
Y
Y
Matsunaga
T
T
Nishida
H
H
Suzuki
Y
Y
Sugiura
A
A
Harwood
H J
HJ
Huang
L H
LH
Kojima
N
N
D000475:Alkenes / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D000818:Animals; D001230:Aspergillus / Q000737:chemistry / Q000145:classification / Q000378:metabolism*; D002176:Candida albicans / Q000187:drug effects; D002851:Chromatography, High Pressure Liquid; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D013186:Farnesyl-Diphosphate Farnesyltransferase / Q000037:antagonists & inhibitors*; D005285:Fermentation; D008401:Gas Chromatography-Mass Spectrometry; D022781:Hepatocytes / Q000187:drug effects; D006801:Humans; D020128:Inhibitory Concentration 50; D007783:Lactones / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D008970:Molecular Weight; D019906:Nuclear Magnetic Resonance, Biomolecular; D051381:Rats; D013055:Spectrophotometry, Infrared; D013056:Spectrophotometry, Ultraviolet
D000475:Alkenes; C447439:CJ-15,183; D004791:Enzyme Inhibitors; D007783:Lactones; D013186:Farnesyl-Diphosphate Farnesyltransferase