AGFD 74 |
| The cytochrome P450 isozymes CYP 1A2 and CYP 2E1 are responsible for the bioactivation of several procarcinogens. Having been reported as cancer chemopreventive agents, the inhibitory effect of a series of naturally occurring methylether analogues of trans-resveratrol, and piceatannol on cytochrome P450 dependent enzymes 7-ethoxyresorufin O-deethylase (EROD) and p-nitrophenol hydroxylase (PNPH) was evaluated in mouse liver microsomes in vitro. The methylether derivatives appear to be potent inhibitors of CYP 1A2, with pterostilbene being the most potent, inhibiting the activity of EROD in a concentration-dependent manner (Ki = 0.39, 0.79, 0.94 and 1.04 µM for pterostilbene, resveratroltrimethylether, pinostilbene and desoxyrhapontigenin, respectively). Pterostilbene, pinostilbene and desoxyrhapontigenin inhibited EROD activity in a mixed (competitive/noncompetitive) manner while resveratroltrimethylether appeared to be a competitive inhibitor of this CYP 1A2 enzymatic marker. Piceatannol was the least potent inhibitor of CYP 1A2 (Ki = 9.67 µM; c.f. resveratrol, Ki = 5.33 µM). Piceatannol, pterostilbene and resveratroltrimethylether in the concentration range from 5 to 100 µM did not inhibit the activity of PNPH, in contrast to resveratrol. Desoxyrhapontigenin was only weakly inhibitory. Pinostilbene was a moderately potent inhibitor of PNPH (IC50 = 72 µM; Ki = 42.6 µM), demonstrating a competitive type of inhibition. Data show that methylation of the hydroxyl groups of resveratrol results to increased inhibition of CYP 1A2 catalytic activity. The 4'-hydroxy group in trans-resveratrol and its analogues may play an important role in the interaction with a binding site and the specific inhibition of CYP 2E1. |
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Sci-Mix
8:00 PM-10:00 PM, Monday, 14 March 2005 Convention Center -- Sails Pavilion, Sci-Mix
Division of Agricultural & Food Chemistry |