title: Stereospecific syntheses of trans-vinyldioxidosqualene and 3-hydroxysulfide derivatives, as potent and time-dependent 2,3-oxidosqualene cyclase inhibitors.
abstract: trans-Vinyldioxidosqualene and beta-hydroxysulfide derivatives were synthesized stereospecifically and evaluated as inhibitors of animal and yeast oxidosqualene cyclases. Only trans-vinyldioxidosqualene and 2,3-epoxy-vinyl-beta-hydroxysulfides, having the reactive function at crucial positions 14,15 and 18,19, were active as inhibitors of animal and yeast cyclases. (14-trans)-28-Methylidene-2,3: 14,15-dioxidoundecanorsqualene 27 was the most potent inhibitor of the series of pig liver cyclase, with an IC50 of 0.4 microM, and it behaved also as the most active time-dependent inhibitor of the animal enzyme.
authors.affiliation: Dipartimento di Scienza e Tecnologia del Farmaco, Università di Torino, Italy.
authors.forename: F
authors.initials: F
authors.lastname: Viola
authors.forename: G
authors.initials: G
authors.lastname: Balliano
authors.forename: P
authors.initials: P
authors.lastname: Milla
authors.forename: L
authors.initials: L
authors.lastname: Cattel
authors.forename: F
authors.initials: F
authors.lastname: Rocco
authors.forename: M
authors.initials: M
authors.lastname: Ceruti
mesh_terms: D000818:Animals; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D019751:Intramolecular Transferases / Q000037:antagonists & inhibitors*; D007700:Kinetics; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry / Q000379:methods; D008862:Microsomes, Liver / Q000201:enzymology; D013185:Squalene / Q000031:analogs & derivatives / Q000138:chemical synthesis*; D013552:Swine
chemical_list: C417191:28-methylidene-2,3-14,15-dioxidoundecanorsqualene; D004791:Enzyme Inhibitors; D013185:Squalene; D019751:Intramolecular Transferases; C021924:lanosterol synthase