Design, Synthesis, and Insecticidal Activity of Isoxazoline Derivatives Incorporating an Acylhydrazine Moiety

Abstract

The long-term use of agricultural insecticides has led to the development of resistant strains. In this context, the isoxazoline structure has become an active area of pesticide research owing to its wide insecticidal spectrum, nontoxicity to mammals, and lack of cross-resistance with known insecticides. In the present study, based on the discovery of compound G22 in our previous work, a series of novel isoxazoline compounds containing acylhydrazine were designed and synthesized using a scaffold hopping strategy. The insecticidal activities of the target compounds were assessed, and compound L17 (LC₅₀ = 0.489 mg/L) showed insecticidal activity against Spodoptera frugiperda superior to those of the commercial insecticides indoxacarb (LC₅₀ = 3.14 mg/L) and fluralaner (LC₅₀ = 0.659 mg/L). Theoretical calculations indicated that the introduction of acylhydrazine plays an important role in the biological activity of the target compounds. Furthermore, the enzyme-linked immunosorbent assay and molecular docking results indicated that L17 may act on the GABA receptor of the target insect. These results indicated that L17 is a potential candidate compound for controlling S. frugiperda populations in agriculture.