Dual α-amylase and α-glucosidase inhibition by 1,2,4-triazole derivatives for diabetes treatment

Abstract The development of effective antidiabetic agents remains a critical challenge in diabetes management. In this study, we introduce novel 1,2,4-triazole-based derivatives designed as dual inhibitors of α-amylase and α-glucosidase, key enzymes in carbohydrate metabolism. Molecular docking iden...

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Main Authors: Mohammed A. Marzouk, Elsayed M. Mahmoud, Wesam S. Shehab, Sherif M. Fawzy, Samar M. Mohammed, Mahmoud Ashraf Abdel-Razek, Ghada E. Khedr, Doaa A. Elsayed
Format: Article
Language:English
Published: Nature Portfolio 2025-07-01
Series:Scientific Reports
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Online Access:https://doi.org/10.1038/s41598-025-11214-4
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Summary:Abstract The development of effective antidiabetic agents remains a critical challenge in diabetes management. In this study, we introduce novel 1,2,4-triazole-based derivatives designed as dual inhibitors of α-amylase and α-glucosidase, key enzymes in carbohydrate metabolism. Molecular docking identified six promising candidates, with compounds 4 and 10 showing the highest potency. Both compounds exhibited strong α-glucosidase inhibition (IC50 = 0.27 ± 0.01 µg/mL and 0.31 ± 0.01 μg/mL, respectively), surpassing acarbose, and also demonstrated potent α-amylase inhibition (IC50 = 0.19 ± 0.01 μg/mL and 0.26 ± 0.01 μg/mL, respectively). Structure–activity relationship analysis highlighted the crucial role of acetyl and bromo substituents in enhancing enzyme inhibition. These findings position triazole-based scaffolds as promising candidates for the development of next-generation antidiabetic therapies.
ISSN:2045-2322