Discovery of Novel Isoxazoline Derivatives Containing Pyrazolamide Fragment as Insecticidal Candidates

Lepidopteran species cause significant harm to agricultural yields and food quality. In this study, a series of innovative isoxazoline derivatives incorporating pyrazolamide moieties were carefully designed and synthesized as potential insecticidal agents. Among these, compound F16 demonstrated an LC₅₀ value of 0.01 mg/L against Plutella xylostella, surpassing that of the lead compound fluxametamide (LC₅₀ = 0.15 mg/L). Furthermore, F16 exhibited broad-spectrum insecticidal activity against Pyrausta nubilalis, Spodoptera frugiperda, Chilo suppressalis, Aphis craccivora, and Sogatella furcifera. Notably, F16 possessed low toxicity against Danio rerio, whereas fluxametamide displayed moderate toxicity. Furthermore, molecular docking analysis demonstrated that the potent insecticidal activity of F16 is likely mediated by its specific interactions with γ-GABA receptors primarily through the formation of hydrogen bonds with key residues. Density functional theory calculations and molecular electrostatic potentials were also performed to gain insights into the insecticidal behavior of F16. These findings suggest that F16 is a promising candidate for further investigation as a novel pesticide.