title: Conjugated methyl sulfide and phenyl sulfide derivatives of oxidosqualene as inhibitors of oxidosqualene and squalene-hopene cyclases.
abstract: Various (1E,3E)- and (1Z,3E)-conjugated methylthio derivatives of oxidosqualene (OS) and conjugated and non-conjugated phenylthio derivatives of OS were obtained. These compounds, designed as inhibitors of pig liver and Saccharomyces cerevisiae 2,3-oxidosqualene-lanosterol cyclases (OSC) (EC 5.4.99.7) and of Alicyclobacillus acidocaldarius squalene-hopene cyclase (SHC) (EC 5.4.99.-), contain the reactive function adjacent to carbons involved in the formation of the third and the fourth cycle during OS cyclization. All the new compounds are inhibitors of OSC and SHC, with various degrees of selectivity. The conjugated methylthio derivatives behaved as potent inhibitors of S. cerevisiae OSC, whereas most of the phenylthio derivatives were especially active toward SHC.
authors.affiliation: Dipartimento di Scienza e Tecnologia del Farmaco, Università degli Studi di Torino, 10125 Torino, Italy.
authors.forename: Flavio
authors.initials: F
authors.lastname: Rocco
authors.forename: Simonetta Oliaro
authors.initials: SO
authors.lastname: Bosso
authors.forename: Franca
authors.initials: F
authors.lastname: Viola
authors.forename: Paola
authors.initials: P
authors.lastname: Milla
authors.forename: Giorgio
authors.initials: G
authors.lastname: Roma
authors.forename: Giancarlo
authors.initials: G
authors.lastname: Grossi
authors.forename: Maurizio
authors.initials: M
authors.lastname: Ceruti
mesh_terms: D000818:Animals; D001406:Bacillaceae / Q000201:enzymology; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D020128:Inhibitory Concentration 50; D019751:Intramolecular Transferases / Q000037:antagonists & inhibitors*; D008099:Liver / Q000201:enzymology; D015394:Molecular Structure; D012441:Saccharomyces cerevisiae / Q000201:enzymology; D013185:Squalene / Q000031:analogs & derivatives* / Q000737:chemistry; D013329:Structure-Activity Relationship; D013440:Sulfides / Q000737:chemistry; D013552:Swine; D013997:Time Factors
chemical_list: C002821:2,3-oxidosqualene; D004791:Enzyme Inhibitors; D013440:Sulfides; D013185:Squalene; D019751:Intramolecular Transferases; C066630:squalene-hopene cyclase; C021924:lanosterol synthase