Inhibition of epoxide hydrolase from human, monkey, bovine, rabbit and murine liver by trans-3-phenylglycidols.
1. trans-3-Phenylglycidols were potent inhibitors of cytosolic epoxide hydrolases in all species tested. 2. The order of inhibitor potency varied from species to species but trans-3-(4-nitrophenyl)glycidols were always the most potent inhibitors tested for cytosolic epoxide hydrolase. 3. The S,S-enantiomer was a more potent cytosolic epoxide hydrolase inhibitor than the R,R-enantiomer when a free hydroxyl group was present. However, (2R,3R)-1-benzoyloxy-2,3-epoxy-3-(4-nitrophenyl)propane was always a better inhibitor than the (2S,3S)-enantiomer. 4. All microsomal epoxide hydrolases were poorly inhibited by the trans-3-phenylglycidols, and related compounds, tested. The best new microsomal epoxide hydrolase inhibitor tested was (1S,2S)-1-phenylpropylene oxide which gave 18-63% inhibition, at 2 mM, depending on the species tested.
Dietze
E C
EC
Department of Entomology and Environmental Toxicology, University of California, Davis 95616.
Casas
J
J
Kuwano
E
E
Hammock
B D
BD
D000328:Adult; D000818:Animals; D002417:Cattle; D003600:Cytosol / Q000201:enzymology; D004851:Epoxide Hydrolases / Q000037:antagonists & inhibitors*; D004852:Epoxy Compounds / Q000494:pharmacology*; D005260:Female; D000882:Haplorhini; D006801:Humans; D008099:Liver / Q000201:enzymology*; D008297:Male; D051379:Mice; D008862:Microsomes, Liver / Q000201:enzymology; D011817:Rabbits; D013045:Species Specificity
D004852:Epoxy Compounds; D004851:Epoxide Hydrolases