College of Life Sciences, Xinyang Normal University, Tea Plant Biology Key Laboratory of Henan Province, Xinyang 464000, China.
College of Medicine, Xinyang Normal University, Xinyang 464000, China.
J Agric Food Chem. 2024 May 1;72(17):9599-9610. doi: 10.1021/acs.jafc.3c06811. Epub 2024 Apr 22.
In the search for novel succinate dehydrogenase inhibitor (SDHI) fungicides to control , thirty-five novel pyrazole-4-carboxamides bearing either an oxime ether or an oxime ester group were designed and prepared based on the strategy of molecular hybridization, and their antifungal activities against five plant pathogenic fungi were also investigated. The results indicated that the majority of the compounds containing oxime ether demonstrated outstanding antifungal activity against and some compounds also displayed pronounced antifungal activities against and . Particularly, compound exhibited the most promising antifungal activity against with an EC value of 0.039 μg/mL, which was about 20-fold better than that of boscalid (EC = 0.799 μg/mL) and 4-fold more potent than fluxapyroxad (EC = 0.131 μg/mL). Moreover, the results of the detached leaf assay showed that compound could suppress the growth of in rice leaves with significant protective efficacies (86.8%) at 100 μg/mL, superior to boscalid (68.1%) and fluxapyroxad (80.6%), indicating promising application prospects. In addition, the succinate dehydrogenase (SDH) enzymatic inhibition assay revealed that compound generated remarkable SDH inhibition (IC = 2.04 μM), which was obviously more potent than those of boscalid (IC = 7.92 μM) and fluxapyroxad (IC = 6.15 μM). Furthermore, SEM analysis showed that compound caused a remarkable disruption to the characteristic structure and morphology of hyphae, resulting in significant damage. The molecular docking analysis demonstrated that compound could fit into the identical binding pocket of SDH through hydrogen bond interactions as well as fluxapyroxad, indicating that they had a similar antifungal mechanism. The density functional theory and electrostatic potential calculations provided useful information regarding electron distribution and electron transfer, which contributed to understanding the structural features and antifungal mechanism of the lead compound. These findings suggested that compound could be a promising candidate for SDHI fungicides to control , warranting further investigation.
为了寻找新型琥珀酸脱氢酶抑制剂 (SDHI) 杀菌剂来防治, 基于分子杂交策略, 设计并合成了 35 种新型吡唑-4-甲酰胺类化合物, 这些化合物含有肟醚或肟酯基团。同时, 还研究了它们对五种植物病原真菌的抑菌活性。结果表明, 大多数含有肟醚的化合物对 和 表现出优异的抑菌活性, 一些化合物对 和 也表现出明显的抑菌活性。特别是, 化合物 对 表现出最有前途的抑菌活性, EC 值为 0.039 μg/mL, 约比 boscalid (EC = 0.799 μg/mL) 好 20 倍, 比 fluxapyroxad (EC = 0.131 μg/mL) 强 4 倍。此外, 离体叶片测定结果表明, 化合物 以 100 μg/mL 时在水稻叶片上对 的生长有显著的抑制作用, 保护效率为 86.8%, 优于 boscalid (68.1%) 和 fluxapyroxad (80.6%), 表明具有广阔的应用前景。此外, SDH 酶抑制试验表明, 化合物 对 SDH 产生了显著的抑制作用 (IC = 2.04 μM), 明显强于 boscalid (IC = 7.92 μM) 和 fluxapyroxad (IC = 6.15 μM) 。进一步的扫描电子显微镜 (SEM) 分析表明, 化合物 导致 的菌丝特征结构和形态明显破坏, 造成严重损伤。分子对接分析表明, 化合物 通过氢键相互作用以及 fluxapyroxad 可以与 SDH 结合口袋完全匹配, 表明它们具有相似的抑菌机制。密度泛函理论和静电势计算提供了有关电子分布和电子转移的有用信息, 有助于理解先导化合物的结构特征和抑菌机制。这些发现表明, 化合物 可能是防治 的新型 SDHI 杀菌剂的候选物, 值得进一步研究。
