New Coumarin Derivatives as Potential Neonicotinoid Insecticides Derivatives: Design, Synthesis and Insecticidal Activity

Neonicotinoid is one of the most important insecticides family that acts on the nervous system of insects. However, the detrimental effects of neonicotinoids on non‐target organisms, highlighted the urgent need for the development of novel alternatives. Herein, an AI‐driven identified coumarin insecticidal lead compound from our previous study was further optimized. The target compounds A16 and A18 showed 67.8% and 62.5% insecticidal activity against Aphis craccivora at 100 mg/L, respectively. Docking binding mode analysis demonstrated that A16 and A18 cannot form the water‐bridged hydrogen bond, which may explain the less desirable activity of the compounds. The electrostatic and hydrophobic potential surfaces both revealed the weaker positive electrostatic distribution and relatively poor aqueous solubility resulted in the limited insecticidal potency. In summary, this work provides valuable insights into the structure–activity relationships of coumarin‐based neonicotinoids and advances the development of novel neonicotinoid insecticides.