Quinazolinone derivatives: Synthesis and comparison of inhibitory mechanisms on α-glucosidase

In this study, eight quinazolinone derivatives were designed and synthesized. Their inhibitory activities on α-glucosidase were assessed in vitro. Two compounds: 2-(4-chlorophenyl)-quinazolin-4(3 H )-one (CQ) and 2-(4-bromophenyl)-quinazolin-4(3 H )-one (BQ) were found to be potent inhibitors of α-glucosidase with IC 50 values of 12.5   ±   0.1   μM and 15.6   ±   0.2   μM, respectively. Spectroscopy methods were performed to analyze the inhibitory mechanisms of both compounds on α-glucosidase. The results revealed that they reversibly inhibited α-glucosidase in a non-competitive manner. CQ and BQ could statically quench the fluorescence spectra by formation of an inhibitor-α-glucosidase complex. The interaction between CQ and α-glucosidase depended on hydrogen bonds , electrostatic and hydrophobic force, while the driving force of the binding between BQ and the enzyme was hydrophobic. The docking results showed that BQ was less active than CQ against α-glucosidase because of its weaker interaction with the enzyme. In brief, the quinazolinone derivatives identified in this work were potentially promising candidates for developing as novel anti-diabetic agents.