2. Academic Validation
  3. Synthesis and biological assessment of benzimidazole-acrylonitrile-1,2,3-triazole derivatives as α-glucosidase inhibitors

Synthesis and biological assessment of benzimidazole-acrylonitrile-1,2,3-triazole derivatives as α-glucosidase inhibitors

  • Bioorg Chem. 2025 Jan:154:108060. doi: 10.1016/j.bioorg.2024.108060.
Mahdi Hatamfayazi 1,  Mohammad Mahdavi 2,  Shahram Moradi Dehaghi 3,  Mehdi Khoshneviszadeh 4,  Aida Iraji 5
Affiliations

Affiliations

  • 1 Faculty of Chemistry, Tehran North Branch, Islamic Azad University, Tehran, Iran.
  • 2 Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran.
  • 3 Faculty of Chemistry, Tehran North Branch, Islamic Azad University, Tehran, Iran. Electronic address: shm_moradi@iau-tnb.ac.irb.
  • 4 Department of Medicinal Chemistry, Faculty of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Iran.
  • 5 Stem Cells Technology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran; Department of Persian Medicine, School of Medicine, Research Center for Traditional Medicine and History of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran. Electronic address: iraji@sums.ac.ir.
PMID: 39719821 DOI: 10.1016/j.bioorg.2024.108060
Abstract

In the pursuit of developing potent α-glucosidase inhibitors for managing diabetes, a series of novel benzimidazole-acrylonitrile-1,2,3-triazole derivatives were designed. Sixteen derivatives (12a-p) were synthesized by varying substituents on the phenyl ring of the N-phenylacetamide moiety. Among these, compound 12m emerged as highly effective against α-glucosidase, displaying an IC50 value of 6.0 ± 0.2 μM, significantly outperforming the positive control acarbose (IC50 = 752.0 ± 2.0 μM). The kinetic evaluation revealed that 12m acts as a reversible competitive inhibitor with a Ki value of 4.5 µM. Molecular modeling and dynamics simulations underscored favorable binding energies, highlighting interactions of these compounds with critical Amino acids within the α-glucosidase active site. These findings position 12m as a promising candidate for the development of α-glucosidase inhibitors with potent anti-diabetic potential.

Keywords

1,2,3-Triazole; Acrylonitrile; Benzimidazole; Molecular dynamic simulation; α-Glucosidase.

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