Synthesis, α-glucosidase inhibitory activity, and molecular dynamic simulation of 6-chloro-2-methoxyacridine linked to triazole derivatives
Mehdi Asadi, Mohammad Ahangari, Aida Iraji, Homa Azizian, Ali Nokhbehzaim, Saeed Bahadorikhalili, Somaye Mojtabavi, Mohamad Ali Faramarzi, Ensieh Nasli‐Esfahani, Bagher Larijani, Mohammad Mahdavi, Massoud Amanlou
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 50 values of 98.0 ± 0.3 µM compared with standard drug acarbose (IC 50 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.