New Isoxazoline Cyclopropyl-Picolinamide Derivatives as Potential Insecticides

Isoxazoline insecticides exhibit broad-spectrum insecticidal activity against insect pests. However, the high toxicity to honeybees limits their application in pest management. To explore reducing the toxicity of isoxazoline derivatives to bees, a series of new isoxazoline cyclopropyl-picolinamide derivatives were designed and synthesized. Bioassays revealed that FSA37 showed excellent insecticidal activity against Plutella xylostella, Spodoptera litura, and Spodoptera exigua, with LC₅₀ values of 0.077, 0.104, and 0.198 mg/L, respectively. These results surpass those of fluxametamide, which displayed LC₅₀ values of 0.605, 0.853, and 1.254 mg/L. Furthermore, FSA37 exhibited notable insecticidal activity against Solenopsis invicta. Importantly, bee toxicity studies indicated that FSA37 possesses significantly lower acute oral toxicity compared to fluralaner and fluxametamide. Quantum chemical calculations and molecular docking studies suggest that the cyclopropyl-picolinamide fragment may be crucial for both biological activity and the safety of nontarget organisms. In conclusion, FSA37 represents a promising candidate for a highly effective and environmentally friendly insecticide.