New Isoxazoline Cyclopropyl-Picolinamide Derivatives as Potential Insecticides

Abstract

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 <b>FSA37</b> showed excellent insecticidal activity against <i>Plutella xylostella</i>, <i>Spodoptera litura</i>, and <i>Spodoptera exigua</i>, 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, <b>FSA37</b> exhibited notable insecticidal activity against <i>Solenopsis invicta</i>. Importantly, bee toxicity studies indicated that <b>FSA37</b> 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, <b>FSA37</b> represents a promising candidate for a highly effective and environmentally friendly insecticide.