文献类型：期刊文献

英文题名：Discovery of Novel Pyrazole β-Ketonitrile Derivatives as Broad Spectrum SDHI Fungicides by Introducing a Flexible Motif

作者：Cheng, Liangliang[1];Wang, Hanting[1];Zhou, Cong[1];Qin, Jiawei[1];Li, Zhong[1];Cheng, Jiagao[1,2]

机构：[1]East China Univ Sci & Technol, Sch Pharm, Shanghai Key Lab Chem Biol, Shanghai 200237, Peoples R China;[2]East China Univ Sci & Technol, Sch Biotechnol, State Key Lab Bioreactor Engn, Shanghai 200237, Peoples R China

年份：2025

卷号：73

期号：24

起止页码：14831

外文期刊名：JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY

收录：;EI(收录号：20252318563692);WOS:【SCI-EXPANDED(收录号:WOS:001502203100001)】；

基金：The authors gratefully acknowledge the National Key Research and Development Program of China (2023YFD1700501), National Natural Science Foundation of China (22307039, 22477029), Natural Science Foundation of Shanghai (22ZR1415600) for the financial supports. The authors are very thankful to the GreenTech Laboratory Co. Ltd. (Shanghai, China) for the help with the in vivo activity evaluation.

语种：英文

外文关键词：fungicide; succinate dehydrogenase inhibitors; beta-ketonitriles; molecular docking; molecularflexibility

摘要：Scaffold optimization plays a critical role in the exploration of fungicides with improved potency and an expanded spectrum. In this study, a series of novel pyrazole beta-ketonitrile derivatives were rationally designed and identified as potent broad-spectrum succinate dehydrogenase inhibitor fungicides, through modifying the molecular flexibility via a flexible methylene motif. After stepwise modifications, compounds A21, A24, and A33 displayed a broad spectrum of antifungal activities in vitro against Fusarium graminearum, Sclerotinia sclerotiorum, and Rhizoctonia solani. Especially, compound A33 (EC50 = 0.356 mu g/mL) exhibited comparable in vitro fungicidal activities against F. graminearum to the positive control pydiflumetofen (EC50 = 0.104 mu g/mL). In the greenhouse assay, compound A33 displayed moderate in vivo protective effects against rice blast at 100 mu g/mL, significant in vivo protection against cucumber powdery mildew at 50 mu g/mL, and moderate in vivo protective effects against wheat scab at 200 mu g/mL. The succinate dehydrogenase (SDH) inhibitory assay revealed that A21, A24, and A33 are potent SDH inhibitors with inhibitory concentration values of 0.123, 0.0317, and 0.0709 mu M, respectively. Docking results demonstrated that H-bonds and cation-pi interactions between A33 and residues of Trp173, Tyr91, and Arg46 are important for the binding of compounds within SDH. Our findings revealed that the improvement of flexibility in the pyrazole beta-ketonitrile scaffold is an effective approach to explore novel potent broad-spectrum SDHIs.