文献类型：期刊文献

英文题名：Novel Acaricidal Silico-Containing Pyrazolyl Acrylonitrile Derivatives Identified through Rational Carbon-Silicon Bioisosteric Replacement Strategy

作者：Zhou, Cong[1];Li, Zhong[1];Qian, Xuhong[1,2];Cheng, Jiagao[1];Maienfisch, Peter[1,3]

机构：[1]East China Univ Sci & Technol, Sch Pharm, Shanghai Key Lab Chem Biol, Shanghai 200237, Peoples R China;[2]East China Normal Univ, Sch Chem & Mol Engn, Shanghai 200241, Peoples R China;[3]CreInSol MCB, CH-4118 Rodersdorf, Switzerland

年份：2023

卷号：71

期号：47

起止页码：18239

外文期刊名：JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY

收录：;EI(收录号：20234214923760);WOS:【SCI-EXPANDED(收录号:WOS:001068697100001)】；

基金：The authors gratefully acknowledge the financial support from National Key Research and Development Plan (2022YFD1700501), National Natural Science Foundation of China (21977030), and Natural Science Foundation of Shanghai (22ZR1415600). Thanks for the kind assistance from Greentech Laboratory Co. Ltd. and Syngenta in the acaricidal activity assay.

语种：英文

外文关键词：carbon-siliconbioisosteric replacement; pyrazolylacrylonitrile acaricides; cyenopyrafen; cyetpyrafen; complex II binding site; structure activity relationship; computational modeling

摘要：The identification of novel pyrazolyl acrylonitrile acaricides with improved properties is of great value for the control of phytophagous mites. A series of innovative silicon-containing pyrazolyl acrylonitriles were rationally designed by applying a bioisosteric carbon-silicon replacement strategy and prepared based on novel synthetic methodology. As a result of our research, we discovered compound A25 which possesses outstanding acaricidal activity. With an LC50 value of 0.062 mg/L, compound A25 was found to be 2.3-fold and 1.9-fold more potent than the commercial acaricides cyenopyrafen and cyetpyrafen, respectively. Enzymatic inhibitory assay indicated that the active principle M1 of compound A25 possesses an IC50 value of 2.32 mu M against Tetranychus cinnabarinus SDH, which was about twofold superior compared to the active metabolites of cyenopyrafen (IC50 = 4.72 mu M). Molecular docking study showed that the active metabolites 2 and 3 and their corresponding silicon counterparts form H-bonds and cation-p interaction with the residues of Trp165, Tyr433, and Arg279.