Hybrid-based design and biological evaluation of quinoline-benzoylhydrazine based derivatives as α-glucosidase inhibitors

Abstract

Diabetes mellitus, especially type 2 diabetes, is a metabolic disease that progresses with time and requires efficient management to avoid long-term problems. One promising approach to target Diabetes mellitus is to inhibit α-glucosidase to control postprandial hyperglycemia. In this work, new quinoline-benzoylhydrazine (7a–m) are designed, synthesized, and evaluated as possible α-glucosidase inhibitors. The Vilsmeier–Haack reaction was used in a multi-step process to synthesize the derivatives, and their inhibitory properties were evaluated. Kinetic analyses of the potent analog were conducted. Critical hydrogen bonding and π-π stacking interactions indicate the substantial binding affinity of the potent analog into the enzyme’s active site, as demonstrated by molecular docking and molecular mechanics with generalised born and surface area solvation (MM/GBSA) simulations. Furthermore, molecular dynamics simulations of the most potent analogs provided insights into their stability and interaction dynamics with the enzyme. These findings suggest that the designed derivatives are promising leads for developing novel α-glucosidase inhibitors to manage type 2 diabetes effectively.