Synthesis and Biological Evaluation of Novel 1,2,4-Triazole Derivatives Containing Amino Acid Fragments

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 contain...

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Bibliographic Details
Main Authors: Haoran Shi, Mingxu Li, Zhenghong Zhou, Aidang Lu, Ziwen Wang
Format: Article
Language:English
Published: MDPI AG 2025-04-01
Series:Molecules
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Online Access:https://www.mdpi.com/1420-3049/30/8/1692
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Summary: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 <sup>1</sup>H-NMR, <sup>13</sup>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 <b>8d</b> and <b>8k</b> exhibited exceptional antifungal activity against <i>Physalospora piricola</i>, with EC<sub>50</sub> values of 10.808 µg/mL and 10.126 µg/mL, respectively. Molecular docking studies demonstrate that the 1,2,4-triazole derivatives <b>8d</b> and <b>8k</b>, 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.
ISSN:1420-3049