Design, synthesis, biological evaluation, DFT and molecular docking studies of novel isoxazolines containing cyclic...

Using a skeleton transition strategy, a series of cyclic amide-containing isoxazoline derivatives were rationally designed and synthesized. Bioassay results revealed that several compounds exhibited potent insecticidal activity and a broad spectrum of action. Notably, compound I-22 showed remarkable insecticidal efficacy against Plutella xylostella and Tetranychus cinnabarinus, with LC₅₀ values of 0.13 mg/L and 0.55 mg/L, respectively, significantly surpassing fluxametamide (LC₅₀ = 0.73 mg/L and 0.81 mg/L, respectively). Moreover, the acute contact toxicity of compound I-22 to honeybees was slightly lower, with an LD₅₀ of 1.46 μg/bee compared to fluxametamide (LD₅₀ = 1.18 μg/bee). Molecular docking studies indicated that both fluxametamide and I-22 act on GABA receptors, and their similar docking conformations may explain the comparable honeybee toxicity. Theoretical calculations further suggested that the 5-ethylpyridine moiety plays a critical role in enhancing insecticidal activity and target selectivity. Collectively, these findings highlight compound I-22 as a promising candidate for the development of a novel isoxazoline insecticide.