文献类型：期刊文献

英文题名：Computational Modeling Oriented Substructure Splicing Application in the Identification of Thiazolidine Derivatives as Potential Low Honeybee Toxic Neonicotinoids

作者：Zhou, Cong[1];Kong, Yijin[1];Zhang, Huihui[2];Zhai, Na[1];Li, Zhong[1];Qian, Xuhong[1,3];Liu, Zewen[2];Cheng, Jiagao[1]

机构：[1]East China Univ Sci & Technol, Sch Pharm, Shanghai Key Lab Chem Biol, Shanghai 200237, Peoples R China;[2]Nanjing Agr Univ, Coll Plant Protect, Key Lab Integrated Management Crop Dis & Pests, Minist Educ, Nanjing 210095, Peoples R China;[3]East China Normal Univ, Sch Chem & Mol Engn, Shanghai 200241, Peoples R China

年份：2024

卷号：72

期号：21

起止页码：11968

外文期刊名：JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY

收录：;EI(收录号：20242116132445);WOS:【SCI-EXPANDED(收录号:WOS:001227280500001)】；

基金：The authors gratefully acknowledge the National Natural Science Foundation of China (21977030), Natural Science Foundation of Shanghai (22ZR1415600), China Postdoctoral Science Foundation (2023M731089), and Postdoctoral Fellowship Program of CPSF (GZC20230806) for the financial supports.

语种：英文

外文关键词：neonicotinoid insecticides; thiazolidine derivatives; insecticidal activity; bee toxicity; acetylcholinebinding protein

摘要：With the aim of identifying novel neonicotinoid insecticides with low bee toxicity, a series of compounds bearing thiazolidine moiety, which has been shown to be low bee toxic, were rationally designed through substructure splicing strategy and evaluated insecticidal activities. The optimal compounds A24 and A29 exhibited LC50 values of 30.01 and 17.08 mg/L against Aphis craccivora, respectively. Electrophysiological studies performed on Xenopus oocytes indicated that compound A29 acted on insect nAChR, with EC50 value of 50.11 mu M. Docking binding mode analysis demonstrated that A29 bound to Lymnaea stagnalis acetylcholine binding protein through H-bonds with the residues of D_Arg55, D_Leu102, and D_Val114. Quantum mechanics calculation showed that A29 had a higher highest occupied molecular orbit (HOMO) energy and lower vertical ionization potential (IP) value compared to the high bee toxic imidacloprid, showing potentially low bee toxicity. Bee toxicity predictive model also indicated that A29 was nontoxic to honeybees. Our present work identified an innovative insecticidal scaffold and might facilitate the further exploration of low bee toxic neonicotinoid insecticides.