title: Microsomal P450-catalyzed N-dealkylation of N,N-dialkylanilines: evidence for a C(alpha)-H abstraction mechanism.
abstract: The early proposal that P450-catalyzed N-dealkylation of N,N-dialkylamines proceeds through a single-electron-transfer (SET) mechanism was later challenged in favor of the C(alpha)-H abstraction mechanism. In the present study, a series of N-alkyl-N-cyclopropyl-p-chloroaniline probes have been used to examine whether the P450-catalyzed N-dealkylations proceed through a C(alpha)-H abstraction and/or a SET mechanism, using phenobarbital-induced rat liver microsomal P450 enzymes as a model system. While the findings are highly consistent with a C(alpha)-H abstraction mechanism, further experimental evidence may be necessary to completely rule out the SET mechanism.
authors.affiliation: Department of Chemistry, Wichita State University, Wichita, Kansas 67260-0051, USA.
authors.forename: Mehul N
authors.initials: MN
authors.lastname: Bhakta
authors.forename: Kandatege
authors.initials: K
authors.lastname: Wimalasena
mesh_terms: D000478:Alkylation; D000814:Aniline Compounds / Q000737:chemistry / Q000378:metabolism*; D000818:Animals; D001665:Binding Sites; D002384:Catalysis; D003577:Cytochrome P-450 Enzyme System / Q000737:chemistry / Q000378:metabolism*; D005290:Ferric Compounds / Q000737:chemistry; D007700:Kinetics; D008862:Microsomes, Liver / Q000201:enzymology; D011725:Pyridines / Q000737:chemistry; D051381:Rats
chemical_list: D000814:Aniline Compounds; D005290:Ferric Compounds; D011725:Pyridines; D003577:Cytochrome P-450 Enzyme System; C023666:pyridine