Synthesis, α-Glucosidase, α-Amylase, and Aldol Reductase Inhibitory Activity with Molecular Docking Study of Novel Imidazo[1,2-a]pyridine Derivatives

Inhibition ofaldose reductase (AR), alpha-glycosidase (alpha-GLY), and alpha-amylase (alpha-AMY) are some of the essential targets in diabetes mellitus (DM). Here, a series of imidazo[1,2-a]pyridine-based 1,3,4-thiadiazole derivatives (8a-k) were successfully synthesized and characterized using 1H NMR, 13C NMR, and HRMS spectroscopic techniques. The inhibition effects of the synthesized derivatives against AR, alpha-GLY, and alpha-AMY were evaluated using both in vitro and in silico methods. In vitro studies revealed that the derivatives (8a-k) showed significant inhibition activity. The results showed that the novel derivatives (8a-k) demonstrated potential inhibitory activity, with K I values covering the following ranges: 23.47 +/- 2.40 to 139.60 +/- 13.33 nM for AR and 6.09 +/- 0.37 to 119.80 +/- 12.31 mu M for alpha-GLY, with IC50 values 81.14 to 153.51 mu M for alpha-AMY. Furthermore, many of these compounds exhibited high inhibition activity, while some of them showed higher potency than the reference compounds. Molecular docking of the target compounds was carried out in the active sites of AR (PDB ID: 4JIR) and alpha-GLY (PDB ID: 5NN8).