Synthesis and Biological Evaluation of Novel 1,2,4-Triazole Derivatives Containing Amino Acid Fragments
Haoran Shi1, Mingxu Li1, Zhenghong Zhou2
1School of Chemical Engineering and Technology, Hebei University of Technology, Tianjin 300401, China.
Abstract:
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 1H-NMR, 13C-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 8d and 8k exhibited exceptional antifungal activity against Physalospora piricola, with EC50 values of 10.808 µg/mL and 10.126 µg/mL, respectively. Molecular docking studies demonstrate that the 1,2,4-triazole derivatives 8d and 8k, 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.
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