title: New verticilides, inhibitors of acyl-CoA:cholesterol acyltransferase, produced by Verticillium sp. FKI-2679.
abstract: Verticillium sp. FKI-2679, a soil isolate, was found to produce inhibitors of acyl-CoA:cholesterol acyltransferase (ACAT) in a cell-based assay using ACAT1- and ACAT2-expressing CHO cells. Three new compounds, verticilides A2, A3 and B1, were isolated along with a known compound, verticilide A1, from the fermentation broth of the fungus by solvent extraction, ODS column chromatography, silica gel column chromatography and preparative HPLC. Structure elucidation showed that these compounds were new cyclic depsipeptide. Verticilides A1, A2, A3 and B1 showed a degree of selectivity towards ACAT2, with IC(50)s 8.5-11-fold more potent than observed against ACAT1.
authors.affiliation: Graduate School of Pharmaceutical Sciences, Kitasato University, 5-9-1 Shirokane, Minato-ku, Tokyo, Japan.
authors.forename: Taichi
authors.initials: T
authors.lastname: Ohshiro
authors.forename: Daisuke
authors.initials: D
authors.lastname: Matsuda
authors.forename: Takeuchi
authors.initials: T
authors.lastname: Kazuhiro
authors.forename: Ryuji
authors.initials: R
authors.lastname: Uchida
authors.forename: Kenichi
authors.initials: K
authors.lastname: Nonaka
authors.forename: Rokuro
authors.initials: R
authors.lastname: Masuma
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Tomoda
mesh_terms: D000818:Animals; D016466:CHO Cells; D002522:Chlorocebus aethiops; D002846:Chromatography, Affinity / Q000379:methods; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D006224:Cricetinae; D003412:Cricetulus; D047630:Depsipeptides / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D005285:Fermentation; D020128:Inhibitory Concentration 50; D012988:Soil Microbiology; D002785:Sterol O-Acyltransferase / Q000037:antagonists & inhibitors*; D020172:Verticillium / Q000378:metabolism*; D000097587:Sterol O-Acyltransferase 2
chemical_list: D047630:Depsipeptides; D004791:Enzyme Inhibitors; D002785:Sterol O-Acyltransferase; D000097587:Sterol O-Acyltransferase 2; C522755:verticilide; C493492:sterol O-acyltransferase 1