Structural Diversity Design, Synthesis, and Insecticidal Activity Analysis of Ester-Containing Isoxazoline Derivatives Acting on the GABA Receptor.

To explore insecticides targeting the γ-aminobutyric acid (GABA) receptor, two series of novel isoxazoline derivatives containing sulfonic and carboxylic esters were designed and synthesized. Their insecticidal activities against Plutella xylostella , Mythimna separata , and Aedes aegypti larvae and their structure-activity relationship were investigated. The sulfonate-containing isoxazoline derivatives ( 10k-q ) exhibited promising insecticidal activities against the three insect larvae. Compound 10o displayed excellent activities with LC 50 values of 8.32, 5.23, and 0.35 μg/mL at 48 h against P. xylostella , M. separata , and A. aegypti larvae, respectively, which were better than or similar to those of avermectin. Furthermore, compound 10o exhibited a faster insecticidal effect than avermectin against M. separata . The mode of action of 10o was preliminarily verified by molecular docking, theoretical calculations, and measurement of glutamate decarboxylase and glutamic pyruvic transaminase activities. Compound 10o is a novel insecticidal candidate acting on GABA receptors, which could guide the discovery of isoxazoline insecticides.