In this work, a total of 36 novel 5-(nicotinamido)-1-phenyl-1H-pyrazole-4-carboxylic acid derivatives were designed and synthesized successfully by introducing a carboxyl group based on the N-(1-(4-chlorophenyl)-4-cyano-1H-pyrazol-5-yl)-6-methoxynicotinamide. Among them, the growth inhibition assays on agar plates showed that compound 5IV-d(5-(2-chloronicotinamido)-1-(p-tolyl)-1H-pyrazole-4-carboxylic acid) exhibited the significant antifungal activity against four important fruit and main crop disease fungi (i.e., Valsa mali Miyabe et Yamada, Botryosphaeria dothidea, Helminthosporium maydis and Rhizoctonia cerealis) with EC50 values of 22.6, 14.5, 17.6 and 18.2 μM, respectively. In addition, 5IV-d showed the excellent inhibitory effect against SDH enzymes with IC50 values ranging from 9.4 to 15.6 μM. In vivo bioassay and molecular docking were applied to explore the potential in practical application and combination of modified structure and SDH. The results of structure-activity relationships indicates that the methoxy substitution at the benzene ring attached to the pyrazole ring and a wide variety of substituents could be responsible for the promising antifungal efficacy of the designed compounds. This study demonstrated that the compound 5IV-d can act as the most potent SDH inhibitor in the reported series of compounds.

中文翻译：

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针对真菌菌株具有优异活性的 SDH 抑制剂的生物活性导向修饰策略

在这项工作中，通过在 N-(1-(4-氯苯基) 基团的基础上引入羧基，共设计并合成了 36 种新型 5-(烟酰胺)-1-苯基-1H-吡唑-4-羧酸衍生物。 )-4-氰基-1H-吡唑-5-基)-6-甲氧基烟酰胺。其中，琼脂平板上的生长抑制试验表明，化合物 5IV-d(5-(2-chloronicotinamido)-1-(p-tolyl)-1H-pyrazole-4-carboxy) 对四种重要的真菌表现出显着的抗真菌活性。水果和主要作物病害真菌（即 Valsa mali Miyabe et Yamada、Botryosphaeria dothidea、Helminthosporium maydis 和 Rhizoctonia绦虫）的 EC50 值分别为 22.6、14.5、17.6 和 18.2 μM。此外，5IV-d对SDH酶显示出优异的抑制作用，IC50值范围为9.4至15.6 μM。应用体内生物测定和分子对接来探索实际应用中的潜力以及修饰结构与SDH的结合。构效关系的结果表明，与吡唑环相连的苯环上的甲氧基取代和多种取代基可能是设计化合物具有良好抗真菌功效的原因。该研究表明，化合物 5IV-d 可以作为报道的系列化合物中最有效的 SDH 抑制剂。构效关系的结果表明，与吡唑环相连的苯环上的甲氧基取代和多种取代基可能是设计化合物具有良好抗真菌功效的原因。该研究表明，化合物 5IV-d 可以作为报道的系列化合物中最有效的 SDH 抑制剂。构效关系的结果表明，与吡唑环相连的苯环上的甲氧基取代和多种取代基可能是设计化合物具有良好抗真菌功效的原因。该研究表明，化合物 5IV-d 可以作为报道的一系列化合物中最有效的 SDH 抑制剂。