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

  • Sci Rep. 2025 Jul 25;15(1):27172. doi: 10.1038/s41598-025-11214-4.
Mohammed A Marzouk  1 ,  Elsayed M Mahmoud  1 ,  Wesam S Shehab  2 ,  Sherif M Fawzy  3 ,  Samar M Mohammed  4 ,  Mahmoud Ashraf Abdel-Razek  5 ,  Ghada E Khedr  6 ,  Doaa A Elsayed  4
Affiliations
  • 1. Department of Pharmaceutical Organic Chemistry, Faculty of Pharmacy, Zagazig University, Zagazig, 44519, Egypt.
  • 2. Department of Chemistry, Faculty of Science, Zagazig University, Zagazig, 44519, Egypt. [email protected].
  • 3. Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Sinai University, Kantara Branch, Al-Ismailia, Egypt.
  • 4. Department of Chemistry, Faculty of Science, Zagazig University, Zagazig, 44519, Egypt.
  • 5. Microbiology and Immunology Department, Faculty of Pharmacy, Zagazig University, Zagazig, 44519, Egypt.
  • 6. Department of Analysis and Evaluation, Egyptian Petroleum Research Institute, Cairo, 11727, Egypt.
PMID: 40715234 DOI: 10.1038/s41598-025-11214-4
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.

Keywords
1,2,4-Triazole derivatives; Anti-diabetic activity; In vitro enzyme inhibition; Molecular docking analysis; α-Amylase inhibitors; α-Glucosidase inhibitors.
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