Metabolism of Chiral Isomers of Isofenphos in the Rat Liver Microsomal System

Abstract

Isofenphos (0-ethyl 0-2-isopropoxycarbonylphenyl isopropylphosphoramidothioate) and isofenphos-oxon show different insecticidal activities to the housefly and the adzuki bean weevil between chiral isomers. The (+)-isomers of both compounds were more toxic than the (-)-isomers. Although 150 values of both chiral isomers of isofenphos-oxon for acetylcholinesterase (ACNE) were higher than 103 M, it was found that the insecticidal activity of isof enphos and its oxon was attributed to the inhibition of ACNE activity after the bioactivation of each chiral isomer with the rat liver microsomal NADPH system. ' It was reported that (+)-cyanofenphos (0-p-cyanophenyl 0-ethyl phenylphosphonothioate) showed more toxic to the housefly and the rice stem borer than the (-)-isomer.2) The (+)-cyanof enphos produced approximately 10-fold larger amounts of cyanof enphos-oxon as an activated metabolite in the rice stem borer than the (-)-isomer. 3) Moreover, it was found that stereoselectivity was dependent on the different metabolism of chiral isomers in organophosphorus compounds, such as S-2571 (0-ethyl 0-2-nitrophenyl isopropylphosphoramidothioate), EPN (0-ethyl 0-p-nitrophenyl phenylphosphonothioate) and fonofos (0-ethyl S-phenyl ethylphosphonodithioate). 4-6) This report is concerned with differential metabolism of the chiral isomers of isofenphos in the rat liver microsomal system. MATERIALS AND METHODS[0-Ethyl-1-14C]isofenphos with 3.

Enantioselective acetylcholinesterase inhibition of the organophosphorous insecticides profenofos, fonofos, and crotoxyphos

“…Results similar to that observed in the present study have been reported in housefly and mice (in vivo) and in bovine erythrocyte, housefly head, and EE‐AChE (in vitro) for profenofos [15,16,26]. In addition, differential metabolism also was demonstrated for the chiral OP, isofenfos, in rat liver microsomes, in which (—)‐isofenfos produced nearly fourfold more oxon than the (+)‐enantiomer, although AChE inhibition and mixed‐function oxidases‐dependent metabolism of the oxon was higher for the (+)‐enantiomer [27].…”