Background: α-Glucosidase is a hydrolyzing enzyme that plays a crucial role in the degradation of carbohydrates and starch to glucose. Hence, α-glucosidase is an important target in carbohydrate mediated diseases such as diabetes mellitus.

Objective: In this study, novel coumarin containing dithiocarbamate derivatives 4a-n were synthesized and evaluated against α-glucosidase in vitro and in silico.

Methods: These compounds were obtained from the reaction between 4-(bromomethyl)-7- methoxy-2H-chromen-2-one 1, carbon disulfide 2, and primary or secondary amines 3a-n in the presence of potassium hydroxide and ethanol at room temperature. In vitro α-glucosidase inhibition and kinetic study of these compounds were performed. Furthermore, a docking study of the most potent compounds was also performed by Auto Dock Tools (version 1.5.6).

Results: Obtained results showed that all the synthesized compounds exhibited prominent inhibitory activities (IC50 = 85.0 ± 4.0-566.6 ± 8.6 μM) in comparison to acarbose as a standard inhibitor (IC50 = 750.0 ± 9.0 μM). Among them, the secondary amine derivative 4d with pendant indole group was the most potent inhibitor. Enzyme kinetic study of the compound 4d revealed that this compound competes with a substrate to connect to the active site of α-glucosidase and therefore is a competitive inhibitor. Moreover, a molecular docking study predicted that this compound interacted with the α-glucosidase active site pocket.

Conclusion: Our results suggest that the coumarin-dithiocarbamate scaffold can be a promising lead structure for designing potent α-glucosidase inhibitors for the treatment of type 2 diabetes.

背景：α-葡萄糖苷酶是一种水解酶，在碳水化合物和淀粉降解为葡萄糖方面起着至关重要的作用。因此，α-葡萄糖苷酶是碳水化合物介导的疾病如糖尿病的重要靶标。

目的：本研究合成了含有二硫代氨基甲酸酯衍生物4a-n的新型香豆素，并在体外和计算机模拟中对α-葡萄糖苷酶进行了评估。

方法：这些化合物是在氢氧化钾和乙醇存在下，于4-（溴甲基）-7-甲氧基-2H-chromen-2-one 1，二硫化碳2与伯或仲胺3a-n反应制得的。室内温度。对这些化合物进行了体外α-葡萄糖苷酶抑制和动力学研究。此外，Auto Dock Tools（版本1.5.6）还对最有效的化合物进行了对接研究。

结果：获得的结果表明，与作为标准抑制剂的阿卡波糖（IC50 = 750.0±9.0μM）相比，所有合成的化合物均显示出显着的抑制活性（IC50 = 85.0±4.0-566.6±8.6μM）。其中，带有吲哚侧基的仲胺衍生物4d是最有效的抑制剂。化合物4d的酶动力学研究表明，该化合物与底物竞争以连接至α-葡糖苷酶的活性位点，因此是竞争性抑制剂。此外，分子对接研究预测该化合物与α-葡萄糖苷酶活性位点口袋相互作用。

结论：我们的结果表明，香豆素-二硫代氨基甲酸酯支架可以作为设计有效的α-葡萄糖苷酶抑制剂用于治疗2型糖尿病的有前途的先导结构。