Discovery of Hydrazine Clubbed Thiazoles as Potential Antidiabetic Agents: Synthesis, Biological Evaluation, and Molecular Docking Studies
Betül Kaya, Hakan Tahtacı, Bilge Çi̇ftci̇, Hatice Esra Duran, Adem Necip, Mesut Işık, Şükrü Beydemir
Abstract
ABSTRACT In this study, hydrazine clubbed thiazole derivatives ( 3a – 3j ) were obtained by Hantzsch thiazole synthesis and characterized by MS, 1 H NMR, and 13 C 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 IC 50 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.