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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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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author Haoran Shi
Mingxu Li
Zhenghong Zhou
Aidang Lu
Ziwen Wang
author_facet Haoran Shi
Mingxu Li
Zhenghong Zhou
Aidang Lu
Ziwen Wang
author_sort Haoran Shi
collection DOAJ
description 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.
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spelling doaj-art-563222aeada942fead26e00cce6610692025-08-20T02:28:20ZengMDPI AGMolecules1420-30492025-04-01308169210.3390/molecules30081692Synthesis and Biological Evaluation of Novel 1,2,4-Triazole Derivatives Containing Amino Acid FragmentsHaoran Shi0Mingxu Li1Zhenghong Zhou2Aidang Lu3Ziwen Wang4School of Chemical Engineering and Technology, Hebei University of Technology, Tianjin 300401, ChinaSchool of Chemical Engineering and Technology, Hebei University of Technology, Tianjin 300401, ChinaState Key Laboratory of Elemento-Organic Chemistry, Research Institute of Elemento-Organic Chemistry, College of Chemistry, Nankai University, Tianjin 300071, ChinaSchool of Chemical Engineering and Technology, Hebei University of Technology, Tianjin 300401, ChinaTianjin Key Laboratory of Structure and Performance for Functional Molecules, College of Chemistry, Tianjin Normal University, Tianjin 300387, ChinaTriazoles 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.https://www.mdpi.com/1420-3049/30/8/1692plant diseasesnovel fungicides1,2,4-triazole derivativesamino acid fragmentsantifungal activities<i>Physalospora piricola</i>
spellingShingle Haoran Shi
Mingxu Li
Zhenghong Zhou
Aidang Lu
Ziwen Wang
Synthesis and Biological Evaluation of Novel 1,2,4-Triazole Derivatives Containing Amino Acid Fragments
Molecules
plant diseases
novel fungicides
1,2,4-triazole derivatives
amino acid fragments
antifungal activities
<i>Physalospora piricola</i>
title Synthesis and Biological Evaluation of Novel 1,2,4-Triazole Derivatives Containing Amino Acid Fragments
title_full Synthesis and Biological Evaluation of Novel 1,2,4-Triazole Derivatives Containing Amino Acid Fragments
title_fullStr Synthesis and Biological Evaluation of Novel 1,2,4-Triazole Derivatives Containing Amino Acid Fragments
title_full_unstemmed Synthesis and Biological Evaluation of Novel 1,2,4-Triazole Derivatives Containing Amino Acid Fragments
title_short Synthesis and Biological Evaluation of Novel 1,2,4-Triazole Derivatives Containing Amino Acid Fragments
title_sort synthesis and biological evaluation of novel 1 2 4 triazole derivatives containing amino acid fragments
topic plant diseases
novel fungicides
1,2,4-triazole derivatives
amino acid fragments
antifungal activities
<i>Physalospora piricola</i>
url https://www.mdpi.com/1420-3049/30/8/1692
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AT zhenghongzhou synthesisandbiologicalevaluationofnovel124triazolederivativescontainingaminoacidfragments
AT aidanglu synthesisandbiologicalevaluationofnovel124triazolederivativescontainingaminoacidfragments
AT ziwenwang synthesisandbiologicalevaluationofnovel124triazolederivativescontainingaminoacidfragments