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 αglucosidase 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
Result:The biological activity results revealed that all of the synthesized compounds showed more potent αglucosidase inhibitory activity in the range of IC50= 57.81±2.16-374.68±15.48 μM when compared to the standard drug
acarbose (IC50= 891.79±6.87 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 57.81±2.16 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
Conclusion: In the light of results, 2 (substitutedphenylamino)quinazolin-4(3H)-one derivatives may serve as lead
compounds to develop novel α-glucosidase inhibitors.