Novel Benzoic Acid Derivatives Bearing Quinazolin-4(3H)-one Ring: Synthesis, Characterization, and Inhibition Effects on α-Glucosidase and α-Amylase

In this study, new benzoic acid derivatives of the quinazolinone ring, which is one of the biologically active members of nitrogen-containing heterocyclic compounds, were synthesized with excellent yields (98-90 %). The structures of the novel compounds (1-12) were characterized with Fourier-transform Infrared (FTIR), Nuclear Magnetic Resonance (H-1 NMR-C-13 NMR), and High-Resolution Mass Spectroscopy (HRMS). alpha-Glucosidase and alpha-Amylase inhibition properties were examined to evaluate the anti-diabetic properties of the synthesized compounds. For alpha-Glucosidase, molecules showed IC50 in ranging of > 100-3.468 & PLUSMN;0.270 mu M and K(i)s in ranging of > 100-3.310 +/- 0.326 mu M. For alpha-Amylase, molecules showed IC50 in ranging of > 100-1.215 &+/- 0.225 mu M. 4-[(2-[(4-phenylpiperazin-1-yl)methyl]-4-oxoquinazolin-3(4H)-ylimino)methyl]benzoicacid (10) has the strongest inhibitory effect for both enzymes. It is 5.4 times more potent inhibitor for alpha-Glucosidase and 34.9 times more potent for alpha-Amylase than the standard inhibitor Acarbose. Also, the molecular docking study was carried out for the most active compound for the determination of ligand-enzyme interactions. Binding affinities of the most active compound were calculated as -5.978 kcal/mol and -5.548 kcal/mol for alpha-Glucosidase and alpha-Amylase, respectively. The aromatic ring and the aminomethyl group of the quinazoline and the carboxyl group moieties have played a critical role in the inhibition.