文献类型：期刊文献

英文题名：Novel Insecticidal Benzo[4,5]imidazo[1,2-b]pyrazole Derivatives Idenatified Through Ring-Closure Scaffold Hopping on Fipronil

作者：Zhou, Cong[1];Li, Guanglong[1];Wang, Sihui[1];Li, Zhong[1];Qian, Xuhong[1,2];Cheng, Jiagao[1]

机构：[1]East China Univ Sci & Technol, Sch Pharm, Shanghai Key Lab Chem Biol, 130 Meilong Rd,POB 544, Shanghai 200237, Peoples R China;[2]East China Normal Univ, Sch Chem & Mol Engn, Shanghai 200241, Peoples R China

年份：2025

卷号：22

期号：3

外文期刊名：CHEMISTRY & BIODIVERSITY

收录：;WOS:【SCI-EXPANDED(收录号:WOS:001356852100001)】；

基金：The authors gratefully acknowledge the National Key Research and Development Program of China (2023YFD1700501), National Natural Science Foundation of China (22307039), Natural Science Foundation of Shanghai (22ZR1415600), China Postdoctoral Science Foundation (2023 M731089), Postdoctoral Fellowship Program of CPSF (GZC20230806) for the financial supports. Thanks for the kind assistance from Shanghai Greentech Laboratory Co., Ltd. in the insecticidal activity assay.

语种：英文

外文关键词：Scaffold hopping; Fipronil; Insecticidal activity; GABARs; Binding mode

摘要：A series of innovative benzo[4,5]imidazo[1,2-b]pyrazole scaffold containing compounds were rationally designed through a ring-closure scaffold hopping strategy and synthetized with an intermediate derivatization approach. Physicochemical properties analysis indicated the potential pesticide-likeness of the target compounds. The optimal target compound A14 showed relatively good insecticidal activity against P. xylostella, with an LC50 value of 37.58 mg/L, and demonstrated lower acute fish toxicity compared to fipronil. Docking binding mode analysis demonstrated that compound A14 bound to GABAR through a H-bond between the amide group and the residue of 6'Thr. The differences in binding modes between benzo[4,5]imidazo[1,2-b]pyrazole target compounds and fipronil may be a key factor for the reduced insecticidal activities. The elucidated binding mode and SAR profile lay a foundation for the further structural optimization of insecticidal benzo[4,5]imidazo[1,2-b]pyrazole derivatives.