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

Inhibition ofaldose reductase (AR), α-glycosidase (α-GLY), and α-amylase (α-AMY) are some of the essential targets in diabetes mellitus (DM). Here, a series of imidazo[1,2-<i>a</i>]pyridine-based 1,3,4-thiadiazole derivatives (<b>8a</b>-<b>k</b>) were successfully synthesized and characterized using ¹H NMR, ¹³C NMR, and HRMS spectroscopic techniques. The inhibition effects of the synthesized derivatives against AR, α-GLY, and α-AMY were evaluated using both in vitro and in silico methods. In vitro studies revealed that the derivatives (<b>8a</b>-<b>k</b>) showed significant inhibition activity. The results showed that the novel derivatives (<b>8a</b>-<b>k</b>) demonstrated potential inhibitory activity, with <i>K</i> _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 μM for α-GLY, with IC₅₀ values 81.14 to 153.51 μM for α-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 α-GLY (PDB ID: 5NN8).