Inhibition of 2,3-oxidosqualene cyclases.

摘要: Monocyclic and tricyclic compounds possessing a nitrogen atom situated at position corresponding to the carbenium ion of high energy intermediates or transition states involved during cyclization 2,3-oxidosqualene tetra- pentacyclic triterpenes have been synthesized. These were tested as inhibitors cycloartenol, lanosterol-, beta(alpha)-amyrin-cyclases in vitro vivo, their affinity was compared that formerly synthesized 8-aza-bicyclic [Taton et al. (1986) Biochem. Biophys. Res. Commun. 138, 764-770]. A monocyclic N-alkyl-hydroxypiperidine shown be strongest inhibitor series upon cycloartenol-cyclase (I50 = 1 microM) from maize embryos but much less effective on Rubus fruticosus suspension cultures pea cotyledons. In contrast, 13-aza-tricyclic derivatives displayed little inhibition cycloartenol-, beta(alpha)-amyrin-cyclases. The obtained data exemplify differences existing process between cycloartenol- (lanosterol-) cyclases one hand other. results are discussed with respect current mechanisms postulated for cyclization. Because its activity vivo appears potent promising tool study sterol biosynthesis regulation.