title: CJ-15,183, a new inhibitor of squalene synthase produced by a fungus, Aspergillus aculeatus.
abstract: 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.
authors.affiliation: Exploratory Medicinal Sciences, PGRD, Nagoya Laboratories, Pfizer Pharmaceuticals Inc., Aichi, Japan. shuzo.watanabe@japan.pfizer.com
authors.forename: S
authors.initials: S
authors.lastname: Watanabe
authors.forename: H
authors.initials: H
authors.lastname: Hirai
authors.forename: M
authors.initials: M
authors.lastname: Ishiguro
authors.forename: T
authors.initials: T
authors.lastname: Kambara
authors.forename: Y
authors.initials: Y
authors.lastname: Kojima
authors.forename: T
authors.initials: T
authors.lastname: Matsunaga
authors.forename: H
authors.initials: H
authors.lastname: Nishida
authors.forename: Y
authors.initials: Y
authors.lastname: Suzuki
authors.forename: A
authors.initials: A
authors.lastname: Sugiura
authors.forename: H J
authors.initials: HJ
authors.lastname: Harwood
authors.forename: L H
authors.initials: LH
authors.lastname: Huang
authors.forename: N
authors.initials: N
authors.lastname: Kojima
mesh_terms: 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
chemical_list: D000475:Alkenes; C447439:CJ-15,183; D004791:Enzyme Inhibitors; D007783:Lactones; D013186:Farnesyl-Diphosphate Farnesyltransferase