Synthesis, Molecular Docking, and In-Vitro Evaluation of Novel 2 - Amino Substituted Benzothiazole Derivatives as Alpha -Glucosidase Inhibitors for Antidiabetic Activity

Abstract

Type 2 diabetes mellitus (T2DM) is a chronic metabolic disorder characterized by persistent hyperglycemia resulting from impaired insulin secretion and insulin resistance. Inhibition of α-glucosidase is an effective therapeutic strategy for reducing postprandial blood glucose levels. In the present study, a series of novel benzothiazole–thiazolidinedione derivatives were synthesized and evaluated for their potential as α-glucosidase inhibitors through molecular docking and in vitro enzymatic assays. The target compounds were synthesized via a multistep synthetic route and characterized using standard physicochemical and spectroscopic techniques. Molecular docking studies were performed against the α-glucosidase enzyme (PDB ID: 3A4A) using AutoDockVina to investigate binding affinity and interactions within the enzyme active site. The synthesized compounds were subsequently evaluated for their α-glucosidase inhibitory activity using the p-nitrophenyl-α-D-glucopyranoside (pNPG) assay, with acarbose employed as the reference standard. Several derivatives exhibited favorable binding affinities and established significant hydrogen bonding and hydrophobic interactions with key catalytic amino acid residues. The in vitro studies demonstrated promising α-glucosidase inhibitory activity, with selected compounds showing inhibition comparable to that of acarbose. The correlation between molecular docking and biological evaluation suggests that the synthesized benzothiazole–thiazolidinedione derivatives possess considerable potential as lead molecules for the development of novel antidiabetic agents. Further pharmacological and in vivo investigations are warranted to establish their therapeutic efficacy and safety.