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

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

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. Mahdavi_chem@yahoo.com.
  • 12 Department of Medicinal Chemistry, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Islamic Republic of Iran. amanlou@tums.ac.ir.
  • 13 Experimental Medicine Research Center, Tehran University of Medical Sciences, Tehran, Islamic Republic of Iran. amanlou@tums.ac.ir.
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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