Aryl-quinoline-4-carbonyl hydrazone bearing different 2-methoxyphenoxyacetamides as potent α-glucosidase inhibitors; molecular dynamics, kinetic and structure–activity relationship studies
Haleh Hamedifar, Mahroo Mirfattahi, Minoo Khalili Ghomi, Homa Azizian, Aida Iraji, Milad Noori, Ali Moazzam, Navid Dastyafteh, Ali Nokhbehzaim, Katayoun Mehrpour, Shahrzad Javanshir, Somayeh Mojtabavi, Mohammad Ali Faramarzi, Bagher Larijani, Mir Hamed Hajimiri, Mohammad Mahdavi
Abstract
Abstract Regarding the important role of α-glucosidase enzyme in the management of type 2 diabetes mellitus, the current study was established to design and synthesize aryl-quinoline-4-carbonyl hydrazone bearing different 2-methoxyphenoxyacetamide ( 11a – o ) and the structure of all derivatives was confirmed through various techniques including IR, 1 H-NMR, 13 C-NMR and elemental analysis. Next, the α-glucosidase inhibitory potentials of all derivatives were evaluated, and all compounds displayed potent inhibition with IC 50 values in the range of 26.0 ± 0.8–459.8 ± 1.5 µM as compared to acarbose used as control, except 11f and 11l . Additionally, in silico-induced fit docking and molecular dynamics studies were performed to further investigate the interaction, orientation, and conformation of the newly synthesized compounds over the active site of α-glucosidase.