Discovery of Novel Isoxazoline Derivatives Containing Benzamide with High Insecticidal Activity.

Insecticide misuse has caused pest resistance, stressing the need for novel pesticides. The isoxazoline structure offers broad-spectrum effectiveness, mammalian safety, and no cross-resistance. Developing efficient insecticides with this scaffold remains challenging. Based on the lead compound , 31 novel isoxazoline compounds with benzamide were made and evaluated for insecticidal efficacy and mechanisms, all showing efficacy against . Especially, , designed based on the three-dimensional quantitative structure-activity relationship (3D-QSAR), displayed activity with LC values of 0.135 mg/L and 0.697 mg/L against and , which were superior to those of fluxametamide (LC = 0.942 and 2.09 mg/L). Pot experiment revealed that was superior on cabbage seedlings than fluxametamide. Theoretical calculations emphasized benzamide's importance for biological activity. Transcriptomic analysis, molecular docking, and enzyme-linked immunosorbent assay suggested that potentially affects the nervous system and GABA receptors of . This study presents a promising candidate for agricultural use.