Discovery of Hydrazine Clubbed Thiazoles as Potential Antidiabetic Agents: Synthesis, Biological Evaluation, and Molecular Docking Studies

Abstract

In this study, hydrazine clubbed thiazole derivatives (3a-3j) were obtained by Hantzsch thiazole synthesis and characterized by MS, 1H NMR, and 13C NMR. The inhibitory potentials of the derivatives against diabetes-related enzymes such as aldose reductase (AR), alpha-glycosidase (alpha-GLY), and alpha-amylase (alpha-AMY) were experimentally determined, and the results were supported by molecular docking. The results showed that the derivatives (3a-3j) displayed varied degree of potential inhibitory activity, with KI values covering the following ranges: 5.47 +/- 0.53 to 23.89 +/- 1.46 nM for AR and 1.76 +/- 0.01 to 24.81 +/- 0.15 mu M for alpha-GLY, and with IC50 values 4.94-28.17 mu M for alpha-AMY, as compared to standard epalrestat and acarbose (KI: 34.53 +/- 2.52 nM for AR and 23.53 +/- 2.72 mu M for alpha-GLY, respectively). The selective activity of these derivatives on antidiabetic enzymes may be important for the treatment of diabetes and may lead to the development of alternative new compounds for this purpose.