2. Academic Validation
  3. 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

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

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. mhrastegar2@yahoo.com.
  • 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. momahdavi@tums.ac.ir.
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.

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