文献类型：期刊文献

英文题名：Rational Design of β-Ketonitrile Acaricides through Binding-Mode-Guided Isosteric Ring Replacement

作者：Zhou, Cong[1];Ge, Jingwen[1];Li, Zhong[1];Qian, Xuhong[1,2];Maienfisch, Peter[1,3];Cheng, Jiagao[1,4]

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, Aegertenstr 21, CH-4118 Rodersdorf, Switzerland;[4]East China Univ Sci & Technol, Sch Biotechnol, State Key Lab Bioreactor Engn, Shanghai 200237, Peoples R China

年份：2026

卷号：74

期号：1

起止页码：478

外文期刊名：JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY

收录：;EI(收录号：20260319926902);WOS:【SCI-EXPANDED(收录号:WOS:001649837400001)】；

基金：The authors gratefully acknowledge the financial support from the National Natural Science Foundation of China (22477029 and 22307039) and the Shanghai Agriculture Applied Technology Development Program (T2024302). Thanks for the kind assistance from Greentech Laboratory Co. Ltd. in the acaricidal activity assay.

语种：英文

外文关键词：beta-ketonitrile acaricide; isosteric ring replacement; structure activity relationship; mode of action; computational modeling

摘要：beta-Ketonitrile acaricides represent one of the most important acaricide classes targeting mite succinate dehydrogenase (SDH). The research of novel beta-ketonitrile acaricidal derivatives is of great value for efficient management of phytophagous mites. Herein, a binding mode similarity-based isosteric ring replacement strategy was applied to the rational design of arylcarbonitrile and arylacrylonitrile target compounds containing SDHI fungicidal active ring moieties. The 3-trifluoromethyl-1H-methylpyrazole moiety containing optimal target compound A23 not only exhibited outstanding acaricidal activities against all developmental stages of Tetranychus cinnabarinus, with an LC50 of 0.105 mg/L against adult populations, 0.087 mg/L against nymphs, and 0.849 mg/L against eggs, respectively, but also demonstrated a 3.2-fold decreased acute fish toxicity compared to cyenopyrafen. Mechanisms of action studies, including SDH inhibitory activity assay and computational binding mode analysis, revealed that the active metabolites of target compounds exerted inhibitory effects through conserved cation-pi interaction and H-bonds within SDH. The optimal target compound showed promising improved acaricidal activity and an ecological safety profile, providing a potential candidate for the further development of beta-ketonitrile acaricide and useful information for the rational design of other SDHI agrochemicals.