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

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), α-glycosidase (α-GLY), and α-amylase (α-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 K_I 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 μM for α-GLY, and with IC₅₀ values 4.94-28.17 μM for α-AMY, as compared to standard epalrestat and acarbose (K_I: 34.53 ± 2.52 nM for AR and 23.53 ± 2.72 μM for α-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.