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

Mehdi Asadi, Ensieh Nasli-Esfahani, Homa Azizian, Mohammad Mahdavi, Aida Iraji, Bagher Larijani, Massoud Amanlou, Mohammad Mehdi Ahangari, Ali Nokhbehzaim, Saeed Bahadorikhalili, Somaye Mojtabavi, Mohamad Ali Faramarzi

Journal: Scientific reports 2024;14(1):17338

PMID: 39069559

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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 IC values of 98.0 ± 0.3 µM compared with standard drug acarbose (IC 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.

Address: Razi Drug Research Center, Iran University of Medical Sciences, Tehran, Islamic Republic of Iran.; Department of Medicinal Chemistry, School of Pharmacy, Iran University of Medical Sciences, Tehran, Islamic Republic of Iran.; Department of Medicinal Chemistry, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Islamic Republic of Iran.; Stem Cells Technology Research Center, Shiraz University of Medical Sciences, Shiraz, Islamic Republic of Iran.; Central Research Laboratory, Shiraz University of Medical Sciences, Shiraz, Islamic Republic of Iran.; Department of Medicinal Chemistry, Faculty of Pharmacy, Alborz University of Medical Sciences, Karaj, Islamic Republic of Iran.; Department of Electronic Engineering, Universitat Rovira I Virgili, 43007, Tarragona, Spain.; Department of Pharmaceutical Biotechnology, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Islamic Republic of Iran.; Diabetes Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Islamic Republic of Iran.; Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Islamic Republic of Iran.; Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Islamic Republic of Iran. [email protected].; Department of Medicinal Chemistry, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Islamic Republic of Iran. [email protected].; Experimental Medicine Research Center, Tehran University of Medical Sciences, Tehran, Islamic Republic of Iran. [email protected].

DOI: 10.1038/s41598-024-68176-2

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MeSH Terms: Glycoside Hydrolase Inhibitors, Triazoles, Molecular Dynamics Simulation, alpha-Glucosidases, Acridines, Kinetics, Molecular Docking Simulation, Structure-Activity Relationship, Humans