Stereochemical considerations on the inhibition of hepatic epoxide hydrolase by some pesticides and their epoxides

The present studies identify the steric factors involved in the hydration of epoxide intermediates of some pesticides by hepatic epoxide hydrolase. Investigations were carried out regarding the formation of reactive epoxide intermediates and their different interactions with the hepatic epoxide hydrolase. Some pesticides and their parent epoxides were selected on he basis of the steric hindrance on the oxirane ring. The results indicate that the inhibition of this enzyme depends on the steric hindrance produced by substituents on the oxirane ring of these pesticides. Mono- and di-substituted oxiranes are good substrates of the epoxide hydrolase and non-competitive inhibitors of the hydration of styrene oxide, while tri-substituted epoxides are virtually inactive on inhibiting the hepatic epoxide hydrolase activity.