Quantitative structure-activity studies of benzoylphenylurea larvicides: VIII. Inhibition of N-acetylglucosamine incorporation into the cultured integument of Chilo suppressalis Walker

Abstract

The inhibition by N-(2,6-disubstituted benzoyl)- N′-(4-substituted phenyl)urea larvicides of the incorporation of N-acetyl-[1- 14C]glucosamine, the precursor of chitin, into cultured fragments of the integument of Chilo suppressalis Walker larvae was measured in terms of the median inhibitory concentration with and without metabolic inhibitors. Variations in the activity index were quantitatively analyzed with physicochemical substituent parameters and regression analysis. The variations in the inhibitory activity of compounds in which ortho substituents on the benzoyl moiety were varied with a fixed substituent in the anilide moiety corresponded with the variations in their larvicidal activity. After separate consideration of the hydrophobic effect participating in transport processes, substituents in the anilide moiety showed peculiar electronic effects that depended upon the situation. Without an inhibitor of oxidative metabolism, the greater the inductive component of the electron-withdrawing property, the greater was the inhibition. This pattern resembled that found in earlier observations of larvicidal activity. With the inhibitor, the greater the total electrondonating property, including both inductive and resonance components, the greater was the inhibition. These results showed that the regular electron-donating effect of substituents in the anilide moiety is intrinsically favorable to the inhibition. Such an electronic mechanism as free-radical intermediate formation at the anilide moiety in oxidative metabolism may not be eliminated completely under the conditions used here for larvicidal activity measurement even with an inhibitor of oxidative metabolism.