Dealkylation of N-nitrosodibenzylamine by metalloporphyrin/oxidant model systems for cytochrome P450.
N-Nitrosodialkylamines are alkylating carcinogens which are metabolically activated to alpha-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-nitrosodialkylamine undergoes oxidation to alpha-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.
Okochi
E
E
Kyoritsu College of Pharmacy, Tokyo, Japan.
Mochizuki
M
M
D001547:Benzaldehydes / Q000032:analysis; D001555:Benzene Derivatives / Q000378:metabolism; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D003640:Dealkylation; D007462:Iodobenzenes / Q000378:metabolism; D008665:Metalloporphyrins / Q000378:metabolism*; D008670:Metals / Q000378:metabolism; D008934:Mitogens / Q000378:metabolism*; D008954:Models, Biological; D009602:Nitrosamines / Q000378:metabolism*; D016877:Oxidants / Q000378:metabolism*; D010084:Oxidation-Reduction; D010545:Peroxides / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D020122:tert-Butylhydroperoxide
D001547:Benzaldehydes; D001555:Benzene Derivatives; D007462:Iodobenzenes; D008665:Metalloporphyrins; D008670:Metals; D008934:Mitogens; D009602:Nitrosamines; D016877:Oxidants; D010545:Peroxides; D017382:Reactive Oxygen Species; C015395:N-nitrosodibenzylamine; D003577:Cytochrome P-450 Enzyme System; D020122:tert-Butylhydroperoxide; C007164:cumene hydroperoxide; C032175:benzaldehyde; C037276:iodosobenzene