Bio-Agriculture Institute of Shaanxi, Xi'an 710043, Shaanxi, People's Republic of China.
Shaanxi Key Laboratory of Plant Nematology, Xi'an 710043, Shaanxi, People's Republic of China.
J Agric Food Chem. 2024 Sep 25;72(38):20850-20861. doi: 10.1021/acs.jafc.4c04078. Epub 2024 Sep 17.
Replacing old pesticides with new pesticide varieties has been the main means to solve pesticide resistance. Therefore, it is necessary to research and develop new antifungal agents for plant protection. In this study, a series of pyridinecarbaldehyde phenylhydrazone derivatives were designed and evaluated for their inhibition activity on plant pathogenic fungi to search for novel fungicide candidates. Picolinaldehyde phenylhydrazone () and nicotinaldehyde phenylhydrazone () were identified as promising antifungal lead scaffolds. The 4-fluorophenylhydrazone derivatives ( and ) of and showed highly effective and broad-spectrum inhibition activity in vitro on 11 phytopathogenic fungi with EC values of 0.870-3.26 μg/mL, superior to the positive control carbendazim in most cases. The presence of the 4-fluorine atom on the phenyl showed a remarkable activity enhancement effect. Compound at 300 μg/mL provided almost complete protection against infection of on tomatoes over the post-treatment 9 days and high safety to germination of plant seeds. Furthermore, showed strong inhibition activity with an IC value of 0.506 μg/mL on succinate dehydrogenase in . Molecular docking showed that both and can well bind to the ubiquinone-binding region of SDH by the conventional hydrogen bond, carbon-hydrogen bond, π-π or π-amide interaction, π-alkyl interaction, X---F (X = N, C, or H) interaction, and van der Waal forces. Meanwhile, scanning and transmission electron analysis displayed that destroyed the morphology of mycelium and the structure of the cell membrane of . Fluorescent staining analysis revealed that changed the mitochondrial membrane potential and cell membrane permeability. Thus, pyridinecarbaldehyde phenylhydrazone compounds emerged as novel antifungal lead scaffolds, and and can be considered promising candidates for the development of new agricultural fungicides.
用新型农药品种替代旧农药品种一直是解决抗药性的主要手段。因此，有必要研究和开发新的植物保护用杀菌剂。在本研究中，设计了一系列吡啶甲酰基苯腙衍生物，并评估了它们对植物病原真菌的抑制活性，以寻找新型杀菌剂候选物。皮考啉醛苯腙（）和烟碱醛苯腙（）被鉴定为有前途的抗真菌先导骨架。和的 4-氟苯腙衍生物（和）在体外对 11 种植物病原真菌表现出高度有效和广谱的抑制活性，EC 值为 0.870-3.26μg/mL，在大多数情况下优于阳性对照多菌灵。苯上的 4-氟原子的存在显示出显著的活性增强效果。化合物在 300μg/mL 时，在处理后 9 天内几乎完全防止感染番茄，对植物种子的发芽具有高度安全性。此外，在 SDH 中，化合物以 0.506μg/mL 的 IC 值表现出强烈的抑制活性。分子对接表明，和都可以通过常规氢键、碳氢键、π-π 或 π-酰胺相互作用、π-烷基相互作用、X---F（X=N、C 或 H）相互作用和范德华力，很好地结合到 SDH 的泛醌结合区域。扫描和透射电子分析显示，破坏了菌丝的形态和细胞膜的结构。荧光染色分析表明改变了线粒体膜电位和细胞膜通透性。因此，吡啶甲酰基苯腙类化合物作为新型抗真菌的先导骨架出现，和可以被认为是开发新的农用杀菌剂的有前途的候选物。
