Design, Synthesis, Biological Evaluation and Docking, ADME Studies of Novel Phenylsulfonyl Piperazine Analogues as α-Amylase Inhibitors

Abstract

Diabetes mellitus (DM) stands as one of the most widespread diseases encountered today. It is primarily characterized by diminished insulin levels and heightened blood glucose concentrations. Inhibition of the α-amylase enzyme plays a pivotal role in the management of diabetes mellitus. Piperazine and sulfonamide groups are recognized for their extensive range of biological effects. The current study involved synthesizing five phenylsulfonyl piperazine derivatives. An evaluation of their α-amylase inhibitory capacities was conducted. Phenylsulfonyl piperazine derivatives (compounds 1-5) exhibited notable α-amylase enzymatic inhibition, with compound 4 showing the most substantial potential for inhibition. The inhibitory percentage of compound 4 (80.61±0.62) surpassed that of the standard drug acarbose (78.81±0.02). The molecular docking studies identified compound 4 as possessing the most substantial inhibitory effect on the α-amylase enzyme, with notable binding energy -8.2 kcal/mol. This compound exhibited specific interactions, including π-π stacking and π-anion interactions with key enzyme residues, solidifying its role as a potent inhibitor