Synthesis, α-glucosidase inhibitory activity, and molecular dynamic simulation of 6-chloro-2-methoxyacridine linked to triazole derivatives

  • Sci Rep. 2024 Jul 28;14(1):17338. doi: 10.1038/s41598-024-68176-2.
Mehdi Asadi  1  2 ,  Mohammad Mehdi Ahangari  3 ,  Aida Iraji  4  5 ,  Homa Azizian  1  2 ,  Ali Nokhbehzaim  6 ,  Saeed Bahadorikhalili  7 ,  Somaye Mojtabavi  8 ,  Mohamad Ali Faramarzi  8 ,  Ensieh Nasli-Esfahani  9 ,  Bagher Larijani  10 ,  Mohammad Mahdavi  11 ,  Massoud Amanlou  12  13
Affiliations
  • 1. Razi Drug Research Center, Iran University of Medical Sciences, Tehran, Islamic Republic of Iran.
  • 2. Department of Medicinal Chemistry, School of Pharmacy, Iran University of Medical Sciences, Tehran, Islamic Republic of Iran.
  • 3. Department of Medicinal Chemistry, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Islamic Republic of Iran.
  • 4. Stem Cells Technology Research Center, Shiraz University of Medical Sciences, Shiraz, Islamic Republic of Iran.
  • 5. Central Research Laboratory, Shiraz University of Medical Sciences, Shiraz, Islamic Republic of Iran.
  • 6. Department of Medicinal Chemistry, Faculty of Pharmacy, Alborz University of Medical Sciences, Karaj, Islamic Republic of Iran.
  • 7. Department of Electronic Engineering, Universitat Rovira I Virgili, 43007, Tarragona, Spain.
  • 8. Department of Pharmaceutical Biotechnology, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Islamic Republic of Iran.
  • 9. Diabetes Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Islamic Republic of Iran.
  • 10. Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Islamic Republic of Iran.
  • 11. Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Islamic Republic of Iran. [email protected].
  • 12. Department of Medicinal Chemistry, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Islamic Republic of Iran. [email protected].
  • 13. Experimental Medicine Research Center, Tehran University of Medical Sciences, Tehran, Islamic Republic of Iran. [email protected].
PMID: 39069559 DOI: 10.1038/s41598-024-68176-2
Abstract

Α-glucosidase inhibition can be useful in the management of carbohydrate-related diseases, especially type 2 diabetes mellitus. Therefore, in this study, a new series of 6-chloro-2-methoxyacridine bearing different aryl triazole derivatives were designed, synthesized, and evaluated as potent α-glucosidase inhibitors. The most potent derivative in this group was 7h bearing para-fluorine with IC50 values of 98.0 ± 0.3 µM compared with standard drug acarbose (IC50 value = 750.0 ± 10.5 μM). A kinetic study of compound 7h revealed that it is a competitive inhibitor against α-glucosidase. Molecular dynamic simulations of the most potent derivative were also executed and indicated suitable interactions with residues of the enzyme which rationalized the in vitro results.

Keywords
Acridine; Molecular dynamic simulation; Synthesis; Triazole; α-Glucosidase.
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