Bioactivation of N-Alkyl Substituted Phosphor- amidothioate Insecticides

The insecticidal activity of O-ethyl O-2-isopropoxycarbonylphenyl N-alkylphoshoramidothioates was examined with reference to their activation in biologicalsystems. Toxicity to the adzuki bean weevil varied with different N-alkyl groups. N-isopropylphosphoramidothioate was the most toxic of the compounds tested, and N-unsubstituted, N-methyland N-ethylphosphoramidothioates were more toxic than fenitrothion. However, N-propyl and N-butyl homologs were less active than fenitrothion with the exception of the N-isopropyl homolog. LD50 values of the phosphoramidothioates for the insect were not correlated with in vitro anti-AChE activity of the phosphoramidates. 150 of N-isopropylphosphoramidate for acetylcholinesterases from adzuki bean weevil and bovine serum was higher than 10-3 M. When the phosphoramidothioates and phosphoramidate were incubated with rat liver microsomal system, AChE activity of bovine serum was strongly inhibited in the presence of NADPH. Inhibition of AChE activity was reduced by addition of SKF 525-A to the microsomal system. The compounds became also potent inhibitors for AChE by treatment with m-chloroperbenzoic acid. From these results, it was concluded that phosphoramidothioates and their oxons were activated oxidatively to inhibit AChE by the microsomal system as well as chemical treatment with peracid.