title: In vitro mechanism-based inactivation of cytochrome P450 3A4 by a new constituent of Cinnamomum burmani.
abstract: Cytochrome P450 enzymes play an important role in drug metabolism. Various studies have reported the potential inhibition of these enzymes by natural compounds, leading to possible drug-herb interaction. One study reported that the MeOH extract of Cinnamomum burmani inhibited CYP3A4 in a mechanism-based mode. Further phytochemical investigation on this plant led to the isolation of 17 compounds including 2 new compounds: cinnamic aldehyde cyclic syringylglycerol 1,3-acetal (1) and 5'-hydroxy-5-hydroxymethyl-4'',5''-methylenedioxy-1,2,3,4-dibenzo-1,3,5-cycloheptatriene (2). The isolated constituents were tested for their preincubation time-dependent inhibition of CYP3A4 at 0 and 20 min. Only the new compound 2 showed an increase in the inhibitory activity to >50 % after 20-min preincubation. Further investigations of the inactivation by 2 displayed characteristics of a mechanism-based inactivator, with KI and kappainact values of 7.7 icroM and 0.04 min(-1), respectively.
authors.affiliation: Institute of Natural Medicine, University of Toyama, Toyama, Japan.
authors.forename: Subehan
authors.initials: S
authors.lastname: Subehan
authors.forename: Shigetoshi
authors.initials: S
authors.lastname: Kadota
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Tezuka
mesh_terms: D027424:Cinnamomum / Q000737:chemistry*; D065692:Cytochrome P-450 CYP3A Inhibitors; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D006801:Humans; D007700:Kinetics; D008862:Microsomes, Liver / Q000187:drug effects; D019906:Nuclear Magnetic Resonance, Biomolecular; D010936:Plant Extracts / Q000737:chemistry
chemical_list: D065692:Cytochrome P-450 CYP3A Inhibitors; D004791:Enzyme Inhibitors; D010936:Plant Extracts