Imidazopyridine-Based Thiazole Derivatives as Potential Antidiabetic Agents: Synthesis, In Vitro Bioactivity, and In Silico Molecular Modeling Approach

Abstract

A new series of thiazole derivatives (<b>4a-p</b>) incorporating imidazopyridine moiety was synthesized and assessed for their in vitro potential α-glucosidase potency using acarbose as a reference drug. The obtained results suggested that compounds <b>4a</b> (docking score = -13.45), <b>4g</b> (docking score = -12.87), <b>4o</b> (docking score = -12.15), and <b>4p</b> (docking score = -11.25) remarkably showed superior activity against the targeted α-glucosidase enzyme, with IC₅₀ values of 5.57 ± 3.45, 8.85 ± 2.18, 7.16 ± 1.40, and 10.48 ± 2.20, respectively. Upon further investigation of the binding mode of the interactions by the most active scaffolds with the α-glucosidase active sites, the docking analysis was accomplished in order to explore the active cavity of the α-glucosidase enzyme. The interpretation of the results showed clearly that scaffolds <b>4a</b> and <b>4o</b> emerged as the most potent α-glucosidase inhibitors, with promising excellent binding interactions with the active site of the α-glucosidase enzyme. Furthermore, utilizing a variety of spectroscopic methods, such as ¹H-NMR, ¹³C-NMR, and HREI-MS, the precise structures of the synthesized scaffolds were determined.