Synthesis of novel coumarin-hydrazone hybrids as a-glucosidase inhibitors and their molecular docking studies

Diabetes mellitus is a metabolic disorder and more than 90% of diabetic patients suffer from type-2 diabetes, which is characterized by hyperglycemia. & alpha;-Glucosidase inhibition has become an appropriate approach to tackle high blood glucose levels. The current study was focused on synthesizing coumarin-hydrazone hybrids (7a-i) by using facile chemical reactions. The synthesized compounds were characterized by using 1H-NMR, 13C-NMR, and IR. To evaluate their anti-diabetic capability, all of the conjugates were screened for in vitro & alpha;-glucosidase inhibitory activity to reveal their therapeutic importance. All of the compounds (except 7b) demonstrated significant enzyme inhibitory potential with IC50 values ranging between 2.39-57.52 & mu;M, as compared to the standard inhibitor, acarbose (IC50 = 873.34 & PLUSMN; 1.67 & mu;M). Among them, compound 7c is the most potent & alpha;-glucosidase inhibitor (IC50 = 2.39 & PLUSMN; 0.05 & mu;M). Additionally, molecular docking was employed to scrutinize the binding pattern of active compounds within the & alpha;-glucosidase binding site. The in silico analysis reflects that hydrazone moiety is an essential pharmacophore for the binding of compounds with the active site residues of the enzyme. This study demonstrates that compounds 7c and 7f deserve further molecular optimization for potential application in diabetic management. This study introduces novel coumarin-hydrazone hybrids, assessed for their potential as & alpha;-glucosidase inhibitors to treat diabetes. Compounds checked for & alpha;-glucosidase inhibition and in silico docking was also carried out. Studies suggest promising therapeutic significance and pharmaceutical use.