Synthesis, α‑Glucosidase,\nα‑Amylase,\nand Aldol Reductase Inhibitory Activity with Molecular Docking Study\nof Novel Imidazo[1,2‑<i>a</i>]pyridine Derivatives

Inhibition ofaldose\nreductase (AR), α-glycosidase (α-GLY),\nand α-amylase (α-AMY) are some of the essential targets\nin 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 <sup>1</sup>H NMR, <sup>13</sup>C NMR, and HRMS spectroscopic techniques.\nThe inhibition effects of the synthesized derivatives against AR,\nα-GLY, and α-AMY were evaluated using both in vitro and\nin silico methods. In vitro studies revealed that the derivatives\n(<b>8a</b>–<b>k</b>) showed significant inhibition\nactivity. The results showed that the novel derivatives (<b>8a</b>–<b>k</b>) demonstrated potential inhibitory activity,\nwith <i>K</i><sub>I</sub> values covering the following\nranges: 23.47 ± 2.40 to 139.60 ± 13.33 nM for AR and 6.09\n± 0.37 to 119.80 ± 12.31 μM for α-GLY, with\nIC<sub>50</sub> values 81.14 to 153.51 μM for α-AMY. Furthermore,\nmany of these compounds exhibited high inhibition activity, while\nsome of them showed higher potency than the reference compounds. Molecular\ndocking of the target compounds was carried out in the active sites\nof AR (PDB ID: 4JIR) and α-GLY (PDB ID: 5NN8).