Abstract：
α-Amylase inhibition is vital in controlling diabetic complications. Herein, we have synthesized a hybrid scaffold based on thiazole-chalcone to access α-amylase inhbition. The proposed structures were verified with spectroscopic techniques (UV-vis, FT-IR, 1H-, 13C-NMR, and elemental analysis). The synthesized compounds were evaluated for their α-amylase and antioxidant potential. In vitro hemolytic assay was performed to test biocompatibility of all compounds. Among tested compounds, 4c (IC50= 3.8 µM), 4g (IC50= 14.5 µM), and 4f (IC50= 17.1 µM) were found excellent α-amylase inhibitors. However, none of the tested compounds exhibited significant antioxidant activity. All compounds showed less lysis than Triton X-100, but compounds 4f and 4h had the least lysis at all tested concentrations and were found to be safe for human erythrocytes. Molecular docking study was performed to evaluate the binding interactions of ligands with human pancreatic α-amylase (HPA). The binding score -8.09 to -8.507 kcal/mol revealed strong binding interactions in the ligand-protein complex. The docking results supplemented the observed α-amylase inhibition and hence augment the scaffold to serve as leads for the antidiabetic drug development.
摘要：
抑制α-淀粉酶对控制糖尿病并发症至关重要。在这里，我们已经合成了一种基于噻唑-查尔酮的混合支架，以获得α-淀粉酶的吸收。用光谱技术(UV-vis，FT-IR,1H-,13C-NMR,和元素分析)。评估合成的化合物的α-淀粉酶和抗氧化潜力。进行体外溶血测定以测试所有化合物的生物相容性。在测试的化合物中，4c(IC50=3.8µM),4g（IC50=14.5µM），和4f（IC50=17.1µM）被发现是优异的α-淀粉酶抑制剂。然而,测试的化合物没有表现出显著的抗氧化活性。所有化合物显示出比TritonX-100更少的裂解,但是化合物4f和4h在所有测试浓度下具有最少的裂解,并且发现对于人红细胞是安全的。进行分子对接研究以评估配体与人胰腺α-淀粉酶（HPA）的结合相互作用。-8.09至-8.507kcal/mol的结合评分揭示了配体-蛋白质复合物中的强结合相互作用。对接结果补充了观察到的α-淀粉酶抑制，因此增强了支架，以作为抗糖尿病药物开发的线索。
