文献类型：期刊文献

英文题名：Discovery of Novel Flexible β-Ketonitrile Derivatives Bearing a Biphenyl Moiety as Potential Succinate Dehydrogenase Inhibitors

作者：Cheng, Liangliang[1];Wang, Sihui[1];Zhou, Cong[1];Zhai, Na[1];Wu, Biao[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：41

起止页码：25908

外文期刊名：JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY

收录：;EI(收录号：20254219333447);WOS:【SCI-EXPANDED(收录号:WOS:001584711700001)】；

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

语种：英文

外文关键词：biphenyl; beta-ketonitriles; succinate dehydrogenaseinhibitors; fungicidal activity; molecular docking

摘要：Plant pathogenic fungi pose a significant threat to global agriculture, highlighting an urgent need for the development of novel fungicides due to resistance issues. A series of pyrazole-beta-ketonitrile compounds incorporating a biphenyl structure were designed and synthesized. Notably, compound A37 demonstrated superior potency against Rhizoctonia solani, with an EC50 value of 0.0144 mu g/mL, more potent than the commercial fungicide fluxapyroxad (EC50 = 0.0270 mu g/mL). In vivo assays demonstrated that A37 exhibited good protective activity against rice sheath blight. Enzyme inhibition activity assays revealed that A37 was a potent inhibitor of succinate dehydrogenase (SDH), with an IC50 value of 0.0263 mu M. Docking studies within R. solani SDH indicated that A37 effectively binds into the ubiquinone site mainly through hydrogen-bond and cation-pi and pi-pi interactions. The identified optimal pyrazole-beta-ketonitrile compound A37, containing a biphenyl structural motif, served as a potent lead for further structural optimization as a potential agricultural SDH inhibitor fungicide.