Design, synthesis and insecticidal activity of isoxazoline derivatives containing a 1,2,4‐triazole thioether moiety

BACKGROUND Isoxazoline insecticides have attracted considerable attention because of their potent insecticidal activity and potential for further structural optimization. RESULTS Using fluxametamide as the lead compound and employing an active substructure hybridization strategy, a total of 28 isoxazoline derivatives ( Y1–Y22 and Z1–Z6 ) were designed and synthesized. Bioassay results showed that several compounds exhibited potential insecticidal activity against Plutella xylostella , Spodoptera frugiperda and Ostrinia furnacalis . Specifically, compound Z3 exhibited the lowest nedian lethal concentration (LC 50 ) value against P. xylostella (0.32 μg mL −1 ) among the tested compounds, which was lower than that of fluxametamide (LC 50 = 1.28 μg mL −1 ). Additionally, compound Z2 showed insecticidal activity against S. frugiperda and O. furnacalis , with LC 50 values of 1.73 and 1.96 μg mL −1 , respectively. Structure–activity relationship (SAR) analysis suggested that the electronic and steric effects of the substituents were associated with differences in insecticidal activity. Molecular docking, molecular dynamics simulations (MD), density functional theory (DFT) calculations and 3D‐QSAR (quantitative SAR) analysis also were used to examine the relationship between the structural features of these compounds and their insecticidal activity, providing preliminary information for subsequent structural optimization. CONCLUSION This study showed that isoxazoline derivatives incorporating a 1,2,4‐triazole thioether moiety exhibited potential insecticidal activity. In particular, compounds Z2 and Z3 may be considered for further structural optimization.