Spectral Modification and Catalytic Inhibition of Human Cytochromes P450 1A1, 1A2, 1B1, 2A6, and 2A13 by Four Chemopreventive Organoselenium Compounds

摘要: Several organoselenium compounds including benzyl selenocyanate (BSC), 1,2-phenylenebis(methylene)selenocyanate (o-XSC), 1,3-phenylenebis(methylene)selenocyanate (m-XSC), and 1,4-phenylenebis(methylene)selenocyanate (p-XSC) have been shown to prevent cancers caused by polycyclic aromatic hydrocarbons (PAHs) 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) in experimental animals; these chemical carcinogens are activated human P450 1 2A family enzymes, respectively, carcinogenic metabolites. In this study, we examined whether selenium interact with inhibit enzymes vitro. Four induced reverse Type I binding spectra 1A1, 1A2, 1B1 2A6 2A13. The spectral dissociation constants (K(s)) for the interaction of chemicals were 3.6-5.7 μM; values lower than those seen 1A1 (19-30 μM) or 1A2 (6.3-13 μM). K(s) 2A13 m-XSC BSC both 0.20 very low compared (5.7 (2.0 directly inhibited 7-ethoxyresorufin O-deethylation activities catalyzed IC(50) <1.0 μM, except inhibition (1.3 Coumarin 7-hydroxylation more four 2A6, 0.22-1.4 μM 2.4-6.2 2A6. Molecular docking studies suggest that can be docked into active sites functional groups differ between enzymes.