Frontiers Science Center for New Organic Matter, National Pesticide Engineering Research Center, State Key Laboratory of Elemento-Organic Chemistry, College of Chemistry, Nankai University, Tianjin 300071, P. R. China.
J Agric Food Chem. 2024 Aug 14;72(32):17802-17812. doi: 10.1021/acs.jafc.4c01739. Epub 2024 Aug 2.
Succinate dehydrogenase (SDH) has been considered an ideal target for discovering fungicides. To develop novel SDH inhibitors, in this work, 31 novel benzothiazol-2-ylthiophenylpyrazole-4-carboxamides were designed and synthesized using active fragment exchange and a link approach as promising SDH inhibitors. The findings from the tests on antifungal activity indicated that most of the synthesized compounds displayed remarkable inhibition against the fungi tested. Compound -(2-(((5-chlorobenzo[]thiazol-2-yl)thio)methyl)phenyl)-3-(difluoromethyl)-1-methyl-1-yrazole-4-carboxamide, with EC values against four kinds of fungi tested below 10 μg/mL and against even below 2 μg/mL, showed superior antifungal activity than that of commercial fungicide thifluzamide, and specifically compounds and were found to show preventative potency of 90.6% and 81.3% against , respectively, similar to the positive fungicide thifluzamide. The molecular simulation studies suggested that hydrophobic interactions were the main driving forces between ligands and SDH. Encouragingly, we found that compound can effectively promote the wheat seedlings and the growth of . Our further studies indicated that compound could stimulate nitrate reductase activity in and increase the biomass of plants.
琥珀酸脱氢酶（SDH）一直被认为是发现杀菌剂的理想靶标。为了开发新型 SDH 抑制剂，本工作采用活性片段交换和连接方法，设计并合成了 31 种新型苯并噻唑-2-基噻苯基吡唑-4-甲酰胺，作为有前途的 SDH 抑制剂。抗真菌活性测试结果表明，大多数合成化合物对测试的真菌表现出显著的抑制作用。化合物 -(2-(((5-氯苯并噻唑-2-基)硫基)甲基)苯基)-3-(二氟甲基)-1-甲基-1-吡唑-4-甲酰胺，对四种真菌的 EC 值均低于 10μg/mL，对 的 EC 值甚至低于 2μg/mL，表现出比商业杀菌剂噻呋酰胺更优异的抗真菌活性，特别是化合物 和 对 的预防效果分别达到 90.6%和 81.3%，与阳性杀菌剂噻呋酰胺相当。分子模拟研究表明，疏水相互作用是配体与 SDH 之间的主要驱动力。令人鼓舞的是，我们发现化合物 可以有效促进小麦幼苗和 的生长。我们进一步的研究表明，化合物 可以刺激 中的硝酸还原酶活性，并增加植物的生物量。
