Oxidative Glutathione Conjugation and Its Novel Role in Activation of the Organophosphorus Insecticide Prothiofos

The reaction of prothiofos oxon S-oxide (S-oxide) with glutathione (GSH) by computational chemistry formed GS(EtO)P(O)OC6H3Cl2 and PrS(O)(HO)P(O)OC6H3Cl2 (desethyl S-oxide). Both were produced from (R)p-S-oxide. From the reaction of prothiofos oxon (oxon) with partially purified resistant housefly glutathione S-transferase under oxidation, 2,4-dichlorophenyl phosphate was detected and it was suggested that desethyl S-oxide was produced by in vitro metabolism. Desethyl oxon showed insecticidal activity toward the housefly on injection and inhibited bovine erythrocyte acetylcholinesterase oxidatively, thus showing that desethyl S-oxide, too, was an activated compound. It has become apparent that GSH conjugates the ethyl group of S-oxide to form desethyl S-oxide, and it shows insecticidal activity with S-oxide. © Pesticide Science Society of Japan