Kaya Betül, Tahtacı Hakan, Çiftçi Bilge, Duran Hatice Esra, Necip Adem, Işık Mesut, Beydemir Şükrü
Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Zonguldak Bulent Ecevit University, Zonguldak, Turkey.
Department of Chemistry, Faculty of Science, Karabuk University, Karabuk, Turkey.
Drug Dev Res. 2025 Feb;86(1):e70060. doi: 10.1002/ddr.70060.
In this study, hydrazine clubbed thiazole derivatives (3a-3j) were obtained by Hantzsch thiazole synthesis and characterized by MS, H NMR, and 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 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 values 4.94-28.17 μM for α-AMY, as compared to standard epalrestat and acarbose (K: 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.
在本研究中,通过汉茨希噻唑合成法获得了肼基连接的噻唑衍生物(3a - 3j),并通过质谱(MS)、氢核磁共振(¹H NMR)和碳核磁共振(¹³C NMR)对其进行了表征。通过实验测定了这些衍生物对糖尿病相关酶如醛糖还原酶(AR)、α - 糖苷酶(α - GLY)和α - 淀粉酶(α - AMY)的抑制潜力,分子对接结果也支持了这些实验结果。结果表明,衍生物(3a - 3j)表现出不同程度的潜在抑制活性,其K值范围如下:AR的K值为5.47 ± 0.53至23.89 ± 1.46 nM,α - GLY的K值为1.76 ± 0.01至24.81 ± 0.15 μM,α - AMY的IC值为4.94 - 28.17 μM,与标准药物依帕司他和阿卡波糖相比(AR的K值分别为34.53 ± 2.52 nM,α - GLY的K值为23.53 ± 2.72 μM)。这些衍生物对降糖酶的选择性活性可能对糖尿病治疗具有重要意义,并可能为此开发出替代性新化合物。