Background: α-Glucosidase is an important hydrolytic enzyme playing a vital role in digestion of carbohydrates. It catalyzes the final step of carbohydrates digestion in biological systems and converts unabsorbed oligosaccharides and disaccharides into monosaccharides, thus resulting in hyperglycemia for diabetic patients. In this respect, it has been considered as a therapeutic target for the treatment of type 2 diabetes since the enzyme inhibition delays carbohydrate digestion and monosaccharide absorption and subsequently reduces postprandial plasma glucose levels.

Objective: In this study, fourteen 2-(substitutedphenylamino)quinazolin-4(3H)-one derivatives were synthesized and evaluated for their α-glucosidase inhibitory activities.

Methods: The structures of the synthesized compounds were confirmed by spectral and elemental analyses. The biological activity and enzyme inhibition kinetic studies were performed by spectrophotometrical method using microplate reader. Physicochemical and drug-likeness properties of selected compounds were predicted by in silico method.

Results: The biological activity results revealed that all of the synthesized compounds showed more potent α-glucosidase inhibitory activity in the range of IC₅₀ = 58 ± 2 - 375 ± 15 μM when compared to the standard drug acarbose (IC₅₀ = 892 ± 7 μM). Among the tested compounds, compound 12 bearing chlorine substituent at ortho position on N-phenyl ring displayed the highest inhibition with an IC₅₀ value of 58 ± 2 μM against α-glucosidase. Furthermore, the enzyme inhibition kinetic study of the most active compound 12 indicated that the compound inhibited the α-glucosidase enzyme as uncompetitive with a Ki value of 63.46 μM. On the other hand, physicochemical and drug-likeness properties of selected compounds were predicted by in silico method. According to the results, it can be speculated that synthesized 2-phenylaminoquinazolin-4(3H)-one derivatives possessed favorable drug-likeness and pharmacokinetic profiles.

Conclusion: In the light of results, 2-(substitutedphenylamino)quinazolin-4(3H)-one derivatives may serve as lead compounds to develop novel α-glucosidase inhibitors.

背景：α-葡萄糖苷酶是一种重要的水解酶，在碳水化合物的消化中起着至关重要的作用。它催化生物系统中碳水化合物消化的最后一步，将未被吸收的低聚糖和二糖转化为单糖，从而导致糖尿病患者出现高血糖。在这方面，它被认为是治疗 2 型糖尿病的治疗靶点，因为酶抑制延迟碳水化合物消化和单糖吸收，随后降低餐后血浆葡萄糖水平。

目的：在本研究中，合成了 14 种 2-(取代苯氨基)喹唑啉-4(3H)-one 衍生物并评估了它们的 α-葡萄糖苷酶抑制活性。

方法：合成化合物的结构通过光谱和元素分析确定。使用酶标仪通过分光光度法进行生物活性和酶抑制动力学研究。通过计算机模拟方法预测所选化合物的物理化学和药物相似性。

结果：生物活性的结果表明，所有合成的化合物在IC的范围内呈更有效的α葡萄糖苷酶抑制活性的₅₀ = 58±2 -相对于标准药物阿卡波糖时375±15μM（IC ₅₀ = 892±7微米）。在测试的化合物中，在 N-苯环邻位带有氯取代基的化合物 12 显示出最高的抑制作用，IC ₅₀对 α-葡萄糖苷酶的值为 58 ± 2 μM。此外，最活跃的化合物 12 的酶抑制动力学研究表明，该化合物对 α-葡萄糖苷酶的抑制是非竞争性的，Ki 值为 63.46 μM。另一方面，所选化合物的物理化学和药物相似性是通过计算机方法预测的。根据结果​​，可以推测合成的 2-苯基氨基喹唑啉-4(3H)-one 衍生物具有良好的药物相似性和药代动力学特征。

结论：根据结果，2-(取代苯氨基)喹唑啉-4(3H)-one衍生物可作为开发新型α-葡萄糖苷酶抑制剂的先导化合物。