Phenylsulfonylpiperazines as α-Glucosidase Enzyme Inhibitors: Design, Synthesis, DFT Calculations, Docking and ADME Studies

Abstract

Diabetes mellitus (DM) is one of the most common diseases affecting people all over the world. An important treatment for DM is the inhibition of the α-glucosidase enzyme. A wide range of biological activities of piperazine and sulfonamide moieties are known. In this study, five phenylsulfonyl piperazine derivatives were synthesized. Their inhibitory capacities were evaluated. The analogues (1-5) showed a good degree of inhibition of α-glucosidase enzyme. Compound 1 has the highest inhibition potential for the α-glucosidase enzyme. Its inhibition percentages (83.52±0.41) were higher than the reference molecule quercetin (81.41±0.02). In silico molecular docking studies were performed for the most potent compound 1 for α-glucosidase enzyme to determine possible protein-ligand interactions. Furthermore, a DFT study was carried out for the evaluation of the quantum mechanical and electronic properties. Finally, ADME profiles of the compounds were theoretically analyzed.