Design, synthesis, in vitro, and in silico anti-α-glucosidase assays of N-phenylacetamide-1,2,3-triazole-indole-2-carboxamide derivatives as new anti-diabetic agents

  • Sci Rep. 2024 Jul 9;14(1):15791. doi: 10.1038/s41598-024-66201-y.
Mohammad Hossein Sayahi  1 ,  Samira Zareei  2 ,  Mohammad Halimi  3 ,  Majid Alikhani  4 ,  Ali Moazzam  2 ,  Maryam Mohammadi-Khanaposhtani  5 ,  Somayeh Mojtabavi  6 ,  Mohammad Ali Faramarzi  6 ,  Hossein Rastegar  7 ,  Parham Taslimi  8 ,  Essam H Ibrahim  9  10  11 ,  Hamed A Ghramh  9  10  12 ,  Bagher Larijani  2 ,  Mohammad Mahdavi  13
Affiliations
  • 1. Department of Chemistry, Payame Noor University, Tehran, Iran.
  • 2. Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran.
  • 3. Department of Biology, Babol Branch, Islamic Azad University, Babol, Iran.
  • 4. Department of Internal Medicine, School of Medicine, Rheumatology Research Center Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran.
  • 5. Cellular and Molecular Biology Research Center, Health Research Institute, Babol University of Medical Sciences, Babol, Iran.
  • 6. Department of Pharmaceutical Biotechnology, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.
  • 7. Cosmetic Products Research Center, Iranian Food and Drug Administration, MOHE, Tehran, Iran. [email protected].
  • 8. Department of Biotechnology, Faculty of Science, Bartin University, Bartin, Turkey.
  • 9. Biology Department, Faculty of Science, King Khalid University, P.O. Box 9004, 61413, Abha, Saudi Arabia.
  • 10. Research Center for Advanced Materials Science (RCAMS), King Khalid University, Abha, Saudi Arabia.
  • 11. Blood Products Quality Control and Research Department, National Organization for Research and Control of Biologicals, Cairo, Egypt.
  • 12. Unit of Bee Research and Honey Production, Faculty of Science, King Khalid University, 61413, Abha, Saudi Arabia.
  • 13. Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran. [email protected].
PMID: 38982268 DOI: 10.1038/s41598-024-66201-y
Abstract

In this work, a novel series of N-phenylacetamide-1,2,3-triazole-indole-2-carboxamide derivatives 5a-n were designed by consideration of the potent α-glucosidase inhibitors containing indole and carboxamide-1,2,3-triazole-N-phenylacetamide moieties. These compounds were synthesized by click reaction and evaluated against yeast α-glucosidase. All the newly title compounds demonstrated superior potency when compared with acarbose as a standard inhibitor. Particularly, compound 5k possessed the best inhibitory activity against α-glucosidase with around a 28-fold improvement in the inhibition effect in comparison standard inhibitor. This compound showed a competitive type of inhibition in the kinetics. The molecular docking and dynamics demonstrated that compound 5k with a favorable binding energy well occupied the active site of α-glucosidase.

Keywords
N-Phenylacetamide; 1,2,3-Triazole; Carboxamide; Indole; α-Glucosidase inhibitor.
Products