Shi Haoran, Li Mingxu, Zhou Zhenghong, Lu Aidang, Wang Ziwen
School of Chemical Engineering and Technology, Hebei University of Technology, Tianjin 300401, China.
State Key Laboratory of Elemento-Organic Chemistry, Research Institute of Elemento-Organic Chemistry, College of Chemistry, Nankai University, Tianjin 300071, China.
Molecules. 2025 Apr 10;30(8):1692. doi: 10.3390/molecules30081692.
Triazoles are important fragments in the development of fungicidal compounds. Fungi have gradually developed drug resistance against traditional fungicides due to long-term overuse. Therefore, there is an urgent need to discover new candidate compounds. A series of 1,2,4-triazole derivatives containing amino acid fragments were designed and synthesized based on mefentrifluconazole. All the target compounds were characterized by H-NMR, C-NMR, and HRMS techniques. Their antifungal activities against five kinds of phytopathogenic fungi were evaluated in vitro. The results revealed that most compounds had broad-spectrum fungicidal activities at 50 μg/mL and four compounds exhibited better antifungal activity than the control drug mefentrifluconazole. Interestingly, the synthesized compounds and exhibited exceptional antifungal activity against , with EC values of 10.808 µg/mL and 10.126 µg/mL, respectively. Molecular docking studies demonstrate that the 1,2,4-triazole derivatives and , which incorporate amino acid groups, exhibit strong binding affinity to 14α-demethylase (CYP51). These findings highlight the potential of these compounds as effective antifungal agents.
三唑类化合物是开发杀真菌剂的重要片段。由于长期过度使用，真菌已逐渐对传统杀菌剂产生耐药性。因此，迫切需要发现新的候选化合物。基于联苯三唑醇设计并合成了一系列含氨基酸片段的1,2,4-三唑衍生物。所有目标化合物均通过氢核磁共振、碳核磁共振和高分辨质谱技术进行表征。体外评价了它们对五种植物病原真菌的抗真菌活性。结果表明，大多数化合物在50μg/mL时具有广谱杀菌活性，四种化合物表现出比对照药物联苯三唑醇更好的抗真菌活性。有趣的是，合成的化合物和对表现出优异的抗真菌活性，其半数有效浓度分别为10.808μg/mL和10.126μg/mL。分子对接研究表明，含有氨基酸基团的1,2,4-三唑衍生物和与14α-脱甲基酶（CYP51）表现出很强的结合亲和力。这些发现突出了这些化合物作为有效抗真菌剂的潜力。
