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 <b>F16</b> demonstrated an LC₅₀ value of 0.01 mg/L against <i>Plutella xylostella</i>, surpassing that of the lead compound fluxametamide (LC₅₀ = 0.15 mg/L). Furthermore, <b>F16</b> exhibited broad-spectrum insecticidal activity against <i>Pyrausta nubilalis</i>, <i>Spodoptera frugiperda</i>, <i>Chilo suppressalis</i>, <i>Aphis craccivora</i>, and <i>Sogatella furcifera</i>. Notably, <b>F16</b> possessed low toxicity against <i>Danio rerio</i>, whereas fluxametamide displayed moderate toxicity. Furthermore, molecular docking analysis demonstrated that the potent insecticidal activity of <b>F16</b> 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 <b>F16</b>. These findings suggest that <b>F16</b> is a promising candidate for further investigation as a novel pesticide.