Bioactivation of <i>N</i>-Alkyl Substituted Phosphoramidothioate Insecticides

Abstract

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-methyl-and 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.

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

“…Isofenphos (I), aminoisofenphos (II), isofenphos-oxon (III), desNisopropyl isofenphos (IV), desphenyl isofenphos (V), desN-isopropyl isofenphos-oxon (VI) and desphenyl isofenphos-oxon (VII) were also synthesized by the methods previously reported. 7,8) Preparation of liver microsomes from a male Wistar rat (7 weeks, 180-200 g body weight) and the procedure of metabolism experiment with the microsomal system were shown in the previous reports. 7,8) A microsomal fraction in 1.…”

Quantitative Structure–activity Relationship of a Series of N-Aryl O-Aryl Phosphoramidate Insecticides

“…Stirring was continued for 2 h. The reaction mixture was cooled again at 0ЊC, and 0.05 mol of the anilinic compound was added dropwise and then stirred for 1 h at room temperature [15,16]. Stirring was continued for 2 h. The reaction mixture was cooled again at 0ЊC, and 0.05 mol of the anilinic compound was added dropwise and then stirred for 1 h at room temperature [15,16].…”

“…The phenolic compound (0.05 mol) was added dropwise at 0ЊC to a stirred solution of 8.26 g O-ethyl phosphordichloridate (0.05 mol) and 10.1 g (0.1 mol) triethylamine in benzene. Stirring was continued for 2 h. The reaction mixture was cooled again at 0ЊC, and 0.05 mol of the anilinic compound was added dropwise and then stirred for 1 h at room temperature [15,16]. Solid phenols or anilines were dissolved first in the minimum amount of benzene.…”

“…This persistence frequently posed hazards to species that were fed such foods or were in contact with these pesticides [5,6]. Recently, much attention has been paid to the effect of the alkyl substituents on the nitrogen atom of phosphoramidates [12,13], phosphoramidothionates [13][14][15][16], and phosphoramidothiolates [13,14]. Extensive work has been performed in this area to study the effect of substituted phenyl phosphates [7][8][9], phosphorothiolates [10], phosphonates, hosphonothioates, phosphinates, and phosphinothioates [11] on their insecticidal activity.…”

“…Extensive work has been performed in this area to study the effect of substituted phenyl phosphates [7][8][9], phosphorothiolates [10], phosphonates, hosphonothioates, phosphinates, and phosphinothioates [11] on their insecticidal activity. Recently, much attention has been paid to the effect of the alkyl substituents on the nitrogen atom of phosphoramidates [12,13], phosphoramidothionates [13][14][15][16], and phosphoramidothiolates [13,14]. However, no information exists on the effect of aryl substitution on the nitrogen atom of these systems.…”