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

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

Automated summary

A new series of thiazole derivatives incorporating an imidazopyridine moiety were synthesized and evaluated for their potential alpha-glucosidase activity. Several compounds showed superior activity against the targeted enzyme, with compounds 4a and 4o being the most potent inhibitors. Docking analysis was used to explore the binding mode of these compounds with the active site of alpha-glucosidase. The structures of the synthesized compounds were determined using various spectroscopic methods.