文献类型：期刊文献

英文题名：Hit to lead optimization of carbothioate derivatives as novel succinate dehydrogenase inhibitors using a multistep virtual screening approach

作者：Zhou, Cong[1];Wang, Cong[1];Sun, Xujuan[1];Cheng, Liangliang[1];Shao, Xusheng[1];Xu, Zhiping[1];Xu, Xiaoyong[1];Li, Zhong[1];Qian, Xuhong[1,2];Cheng, Jiagao[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, Peoples R China;[3]East China Univ Sci & Technol, Sch Biotechnol, State Key Lab Bioreactor Engn, Shanghai, Peoples R China

年份：2025

卷号：81

期号：8

起止页码：4373

外文期刊名：PEST MANAGEMENT SCIENCE

收录：;WOS:【SCI-EXPANDED(收录号:WOS:001452568200001)】；

基金：The authors gratefully acknowledge the financial support from the National Key Research and Development Program of China (2023YFD1700501), National Natural Science Foundation of China (22307039, 22477029), and Natural Science Foundation of Shanghai (22ZR1415600). The in vivo fungicidal activities were performed in Greentech Laboratory Co. Ltd. (Shanghai, China).

语种：英文

外文关键词：fungicide; succinate dehydrogenase inhibitors; virtual screening; carbothioates; lead optimization

摘要：BACKGROUND Succinate dehydrogenase inhibitors (SDHIs) represent one of the most important fungicide subclasses for the chemical control of plant diseases. The identification of novel SDHIs with innovative scaffolds through virtual screening is crucial for pathogenic fungi management and food security. RESULTS A novel carbothioate hit compound was identified through a hierarchical virtual screening protocol with novel beta-ketonitrile fungicidal compound as query structure. The structural optimization resulted optimal compound A12 showed good in vitro broad-spectrum fungicidal activities against Rhizoctonia solani, Sclerotiorum sclerotiorum, Botrytis cinerea and Fusarium graminearum, with EC50 values of 4.38, 10.76, 7.69, and 10.28 mu g/mL, respectively. A12 also exhibited promising in vivo protective efficacy against rice sheath blight. Scanning electron microscopy (SEM) observation and SDH enzymatic assays revealed that A12 served as a potent SDH inhibitor, with an IC50 value of 4.53 mu M. Computational binding mode research demonstrated that A12 formed H-bonds, cation-pi and T-pi interaction with SDH. CONCLUSION The identified optimal carbothioate compound A12 served as a potent lead compound for further structural optimization as potential agricultural SDHI fungicides.