Succinate dehydrogenase (SDH), a crucial bridge enzyme between the respiratory electron transfer chain and tricarboxylic acid (or Krebs) cycle, has been identified as an ideal target for the development of effective fungicide. In this study, a series of 24 novel SDH inhibitors (SDHIs) were designed, synthesized, and characterized by ¹H-NMR, ¹³C-NMR, and HRMS. In vitro fungicidal activity experiments, most of the compounds exhibited broad-spectrum antifungal activities against five plant pathogenic fungi. Compounds 9j and 9k showed excellent activities against Pythium aphanidermatum with EC₅₀ values of 9.93 mg/L and 10.50 mg/L, respectively, which were superior to the lead compound Fluopyram with an EC₅₀ value of 19.10 mg/L. Furthermore, the toxicity of these compounds was also tested against Meloidogyne incognita J2 nematodes. The results indicated that compound 9x exhibited moderate nematicidal activity (LC₅₀/48h = 71.02 mg/L). Molecular docking showed that novel guanidine amide of 9j formed hydrogen bonds with crucial residues, which was crucial to the binding of an inhibitor and SDH. This present work indicates that these derivatives may serve as novel potential fungicides targeting SDH.

琥珀酸脱氢酶 (SDH) 是呼吸电子传递链和三羧酸（或三羧酸）循环之间的关键桥梁酶，已被确定为开发有效杀菌剂的理想目标。在本研究中，设计、合成了一系列 24 种新型 SDH 抑制剂 (SDHI)，并通过¹ H-NMR、¹³ C-NMR 和 HRMS 对其进行了表征。在体外杀真菌活性实验中，大多数化合物对五种植物病原真菌表现出广谱抗真菌活性。化合物9j和9k对Pythium aphanidermatum表现出优异的活性，EC 为₅₀值分别为 9.93 mg/L 和 10.50 mg/L，优于先导化合物氟吡菌酰胺，EC ₅₀值为 19.10 mg/L。此外，还测试了这些化合物对南方根结线虫J2 线虫的毒性。结果表明化合物9x表现出中等杀线虫活性(LC ₅₀ /48h = 71.02 mg/L)。分子对接表明，9j 的新型胍酰胺与关键残基形成氢键，这对抑制剂和 SDH 的结合至关重要。目前的工作表明，这些衍生物可以作为靶向 SDH 的新型潜在杀菌剂。