Title:Synthesis and Enzymological Characterization of Some 2-(Substitutedphenylamino) quinazolin-4(3H)-one Derivatives as Potent α-Glucosidase Inhibitors In Vitro
Volume: 18
Issue: 7
Author(s): Emre Kadir Ayan, Zeynep Soyer* Şirin Uysal
Affiliation:
- Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Ege University, 35100 Bornova, Izmir,Turkey
Keywords:
Quinazolin-4(3H)-one, aniline, α-glucosidase inhibitor, diabetes mellitus, kinetic study, synthesis.
Abstract:
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.
