Discovery of Novel Thiazole Carboxamides as Antifungal Succinate Dehydrogenase Inhibitors

作者：Xiaofeng Guo, Bin Zhao, Zhijin Fan, Dongyan Yang, Nailou Zhang, Qifan Wu, Bin Yu, Shuang Zhou, Tatiana A. Kalinina, Nataliya P. Belskaya · 发表于：Journal of Agricultural and Food Chemistry · 年份：2019 · DOI：10.1021/acs.jafc.8b06935 · 被引用次数：95 · 研究领域：Fungal Plant Pathogen Control、Plant-Microbe Interactions and Immunity、Plant Disease Resistance and Genetics

To contribute molecular diversity for novel fungicide development, a series of novel thiazole carboxamides were rationally designed, synthesized, and characterized with the succinate dehydrogenase (SDH) as target. Bioassay indicated that compound 6g showed the similar excellent SDH inhibition as that of Thifluzamide with IC 50 of 0.56 mg/L and 0.55 mg/L, respectively. Some derivatives displayed improved in vitro fungicidal activities against Rhizoctonia cerealis and Sclerotinia sclerotiorum with EC 50 of 1.2–16.4 mg/L and 0.5–1.9 mg/L. Surprisingly, 6g showed promising in vitro fungicidal activities against R. cerealis and S. sclerotiorum with EC 50 of 6.2 and 0.6 mg/L, respectively, which was superior to Thifluzamide with the EC 50 of 22.1 and 4.4 mg/L, respectively. Additionally, compounds 6c and 6g displayed excellent in vivo fungicidal activities against S. sclerotiorum on Brassica napus L. leaves with protective activity of 75.4% and 67.3% at 2.0 mg/L, respectively, while Thifluzamide without activity at 5.0 mg/L. Transcriptomic analysis of S. sclerotiorum treated with 6g by RNA sequencing indicated the down-regulation of succinate dehydrogenase gene SDHA and SDHB, and the inhibition of the TCA-cycle.