Stereospecific syntheses of trans-vinyldioxidosqualene and 3-hydroxysulfide derivatives, as potent and time-dependent 2,3-oxidosqualene cyclase inhibitors.
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.
Viola
F
F
Dipartimento di Scienza e Tecnologia del Farmaco, Università di Torino, Italy.
Balliano
G
G
Milla
P
P
Cattel
L
L
Rocco
F
F
Ceruti
M
M
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
C417191:28-methylidene-2,3-14,15-dioxidoundecanorsqualene; D004791:Enzyme Inhibitors; D013185:Squalene; D019751:Intramolecular Transferases; C021924:lanosterol synthase