Dealkylation of N-Nitrosodibenzylamine by Metalloporphyrin/Oxidant Model Systems for Cytochrome P450

Abstract

N-Nitrosodialkylamines are alkylating carcinogens which are metabolically activated to a-hydroxy nitrosamines through oxidative dealkylation by cytochrome P450. In this study, the dealkylation step in the activation of N-nitrosodibenzylamine (NDBz) was investigated with metalloporphyrin/oxidant model systems under non-aqueous conditions, as biomimetic chemical models of cytochrome P450. In the model systems, NDBz was dealkylated and benzaldehyde was released. The catalytic activity required a porphyrin ring with a central metal that can interact with an oxidant. The oxidative activity of the model varied with the oxidant used in the order of tert-butyl hydroperoxide > cumene hydroperoxide > iodosobenzene, and also with the central metal of porphyrin used in the order of tetraphenylporphyrinatoiron(III) chloride > its manganese derivative. It was confirmed that N-nitro-sodialkylamine undergoes oxidation to α-hydroxy nitrosamine in chemical model systems which are free of protein. These biomimetic models should be useful in elucidating the mechanisms of the metabolism of N-nitrosodialkylamines. © 1995, The Pharmaceutical Society of Japan. All rights reserved.