Structure-Based Discovery of Potential Fungicides as Succinate Ubiquinone Oxidoreductase Inhibitors

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• 作者：Li Xiong ; Hua Li ; Li-Na Jiang ; Jing-Ming Ge ; Wen-Chao Yang ; Xiao Lei Zhu ; Guang-Fu Yang
• 刊名：Journal of Agricultural and Food Chemistry
• 出版年：2017
• 出版时间：February 8, 2017
• 年：2017
• 卷：65
• 期：5
• 页码：1021-1029
• 全文大小：448K
• ISSN：1520-5118

文摘

A series of diphenyl ether-containing pyrazole-carboxamide derivatives was designed and synthesized as new succinate ubiquinone oxidoreductase (SQR) inhibitors. This highly potent molecular scaffold was developed from a moderately activie hit 3, obtained from our previous pharmacophore-linked fragment virtual screening (PFVS) method. The results of greenhouse tests indicated that some analogues showed good SQR inhibitory activity, with promising fungicidal activity against Rhizoctonia solani and Sphaerotheca fuliginea at a dosage of 200 mg/L. Most surprisingly, compound 62 showed the highest SQR inhibitory activity with a K_i value of 0.081 μM, about 4-fold more potent than penthiopyrad (K_i = 0.307 μM). In addition, compounds 43 and 62 displayed excellent fungicidal activity even at a dosage as low as 6.25 mg/L, which was superior to thifluzamide. Moreover, compound 62 exhibited excellent protection effect against R. solani and provided about 81.2% protective control efficancy after 21 days with two sprayings. The present work indicated that these two compounds could be used as potential agricultural fungicides targeting SQR.