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 L17, 31 novel isoxazoline compounds with benzamide were made and evaluated for insecticidal efficacy and mechanisms, all showing efficacy against Plutella xylostella. Especially, M31, designed based on the three-dimensional quantitative structure-activity relationship (3D-QSAR), displayed activity with LC50 values of 0.135 mg/L and 0.697 mg/L against Plutella xylostella and Ostrinia furnacalis, which were superior to those of fluxametamide (LC50 = 0.942 and 2.09 mg/L). Pot experiment revealed that M31 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 M31 potentially affects the nervous system and GABA receptors of P. xylostella. This study presents a promising candidate for agricultural use.