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

Arch Biochem Biophys. 1988 Feb 15;261(1):12-5. doi: 10.1016/0003-9861(88)90098-7.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cimetidine* / metabolism
  • Cytochrome P-450 Enzyme System / metabolism*
  • Hydrogen Peroxide*
  • Hydroxylation
  • Iron Chelating Agents*
  • Iron*
  • Magnetic Resonance Spectroscopy
  • Mass Spectrometry
  • Oxidation-Reduction

Substances

  • Fenton's reagent
  • Iron Chelating Agents
  • Cimetidine
  • Cytochrome P-450 Enzyme System
  • Hydrogen Peroxide
  • Iron