Abstract：
Succinate dehydrogenase inhibitors are essential fungicides used in agriculture. To explore new pyrazole-carboxamides with high fungicidal activity, a series of N-substitutedphenyl-3-di/trifluoromethyl-1-methyl-1H-pyrazole-4-carboxamides bearing a branched alkyl ether moiety were designed and synthesized. The in vitro bioassay indicated that some target compounds displayed appreciable fungicidal activity. For example, compounds 5d and 5e showed high efficacy against S. sclerotiorum with EC50 values of 3.26 and 1.52 μg/mL respectively, and also exhibited excellent efficacy against R. solani with EC50 values of 0.27 and 0.06 μg/mL respectively, which were comparable or superior to penflufen. The further in vivo bioassay on cucumber leaves demonstrated that 5e provided strong protective activity of 94.3 % against S. sclerotiorum at 100 μg/mL, comparable to penflufen (99.1 %). Cytotoxicity assessment against human renal cell lines (239A cell) revealed that 5e had low cytotoxicity within the median effective concentrations. Docking study of 5e with succinate dehydrogenase illustrated that R-5e formed one hydrogen bond and two π-π stacking interactions with amino acid residues of target enzyme, while S-5e formed only one π-π stacking interaction with amino acid residue. This study provides a valuable reference for the design of new succinate dehydrogenase inhibitor.
摘要：
琥珀酸脱氢酶抑制剂是农业中使用的必需杀真菌剂。探索具有高杀菌活性的新型吡唑-甲酰胺,设计并合成了一系列带有支链烷基醚部分的N-取代苯基-3-二/三氟甲基-1-甲基-1H-吡唑-4-甲酰胺。体外生物测定表明，一些目标化合物显示出明显的杀真菌活性。例如,化合物5d和5e对硬核链球菌具有较高的疗效，EC50值分别为3.26和1.52μg/mL，并且还表现出优异的抗R.solani功效，EC50值分别为0.27和0.06μg/mL，与penflufen相当或优于penflufen。对黄瓜叶片的进一步体内生物测定表明，5e在100μg/mL时对硬核链球菌具有94.3％的强保护活性，与penflufen（99.1％）相当。针对人肾细胞系(239A细胞)的细胞毒性评估显示5e在中值有效浓度内具有低细胞毒性。5e与琥珀酸脱氢酶的对接研究表明，R-5e与目标酶的氨基酸残基形成一个氢键和两个π-π堆叠相互作用，而S-5e仅与氨基酸残基形成一个π-π堆叠相互作用。本研究为新型琥珀酸脱氢酶抑制剂的设计提供了有价值的参考。
