文献类型：期刊文献

英文题名：Novel Insecticidal Pyridylhydrazono Derivatives Identified via Scaffold Hopping and Conformation Regulation Strategies

作者：Li, Xiaoyang[1];Zhou, Cong[1];Yang, Wulin[1];Li, Zhong[1];Cheng, Jiagao[1]

机构：[1]East China Univ Sci & Technol, Shanghai Key Lab Chem Biol, Sch Pharm, Shanghai 200237, Peoples R China

年份：2024

卷号：21

期号：12

外文期刊名：CHEMISTRY & BIODIVERSITY

收录：;WOS:【SCI-EXPANDED(收录号:WOS:001377210500019)】；

基金：The authors gratefully acknowledge the financial support from the National Key Research and Development Program of China (2023YFD1700501), Natural Science Foundation of Shanghai (22ZR1415600), National Natural Science Foundation of China (22307039), China Postdoctoral Science Foundation (2023M731089), and Postdoctoral Fellowship Program of CPSF (GZC20230806).

语种：英文

外文关键词：Pymeteozine; Scaffold hopping; Molecular docking; Conformation regulation; Potential energy surface scanning

摘要：Insect transient receptor potential vanilloid (TRPV) channels are critical targets for insecticides. In this study, various scaffold-hopping strategies were employed in the rational design of pyridylhydrazono derivatives as potential insect TRPV channels modulators. Insecticidal bioassay demonstrated that the initial target compounds exhibited lower insecticidal activity compared to pymetrozine, with the optimal compound B3 exhibiting a mortality rate of 53.3% against Aphis craccivora at 400mgL(-1). Conformation analysis indicated that the high energy barrier required for the transition from the lowest-energy conformation to the active conformation may be a key factor contributing to the reduced insecticidal activities of the target compounds. Further structural optimizations aimed at reducing this energy barrier through binding mode-based conformation regulation led to the identification of optimal target 4-(3 '-pyridylhydrazono)pyrazol-5-one derivatives C1 and C2. These compounds exhibited reduced transition energy barriers and improved insecticidal activity, with moderate mortality rate of 66.3% and 75.7% against A. craccivora at 400mgL(-1), respectively. These findings provide valuable insights for future research on the discovery of insect TRPV modulators and have significant implications for the development of more effective agricultural insecticides.