The role of iron chelates on the selectivity of Fenton reagent in hydroxylation, N-demethylation, and sulfoxidation of cimetidine: a novel biomimetic model for the regioselectivity of cytochrome P-450.
The effect of iron chelates on the reaction of cimetidine with Fenton reagent [Fe(II)/H2O2] has been investigated. Iron chelates with high affinity to ferrous ions inhibited this reaction. However, iron chelates with high affinity to ferric ions selectively promote either hydroxylation, N-demethylation, or sulfoxidation of cimetidine. These results indicate that the oxidation of cimetidine with hydrogen peroxide activated by various chelated ferrous ions serves as a biomimetic model for the regioselectivity of multiple forms of cytochrome P-450 in the metabolism of cimetidine.
Zbaida
S
S
Department of Pharmacy, School of Pharmacy, Hebrew University of Jerusalem, Israel.
Kariv
R
R
Fischer
P
P
D002927:Cimetidine / Q000378:metabolism; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D006861:Hydrogen Peroxide; D006900:Hydroxylation; D007501:Iron; D007502:Iron Chelating Agents; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D010084:Oxidation-Reduction
C045076:Fenton's reagent; D007502:Iron Chelating Agents; D002927:Cimetidine; D003577:Cytochrome P-450 Enzyme System; D006861:Hydrogen Peroxide; D007501:Iron