Discovery of Novel Isoxazoline Derivatives Containing Diaryl Ether against Fall Armyworms.

With the continuous evolution of insect resistance, it is a tremendous challenge to control the fall armyworm () with traditional insecticides. To solve this pending issue, a series of novel isoxazoline derivatives containing diaryl ether structures were designed and synthesized, and most of the target compounds exhibited excellent insecticidal activity. Based on the three-dimensional quantitative structure-activity relationship (3D-QSAR) model analysis, we further optimized the molecular structure with compound obtained and tested for its activity. Compound (LC = 1.69 mg/L) exhibited excellent insecticidal activity against , which was better than those of commercial fipronil (LC = 70.78 mg/L) and indoxacarb (LC = 5.37 mg/L). The enzyme-linked immunosorbent assay showed that could upregulate the levels of GABA in insects. In addition, molecular docking and transcriptomic results also indicated that compound may affect the nervous system of by acting on GABA receptors. Notably, through high-performance liquid chromatography (HPLC), we were able to obtain the two enantiomers of compound , and the insecticidal activity test revealed that was 44 times more active than against . This study established the chemistry basis and mechanistic foundations for the future development of pesticide candidates against fall armyworms