Synthesis and Bioactivity Investigation of Novel 2-({2-[(Dialkylamino) Methyl] Quinazolin-4-one-3-yl} Methyl) Benzonitrile Derivatives as Dipeptidyl Peptidase-4 Inhibitory Agent.

Background: Quinazolinone derivatives have been documented to exhibit antidiabetic properties via the mechanism of dipeptidyl peptidase-4 (DPP-4) inhibition. Objectives: To prepare and investigate the DPP-4 inhibitory activity in vitro and in silico of a series of novel 2-({2-[(dialkylamino)methyl]quinazolin-4-one-3-yl}methyl)benzonitrile derivatives. Methods: The compounds were synthesized, and the chemical structures were confirmed through spectroscopic techniques. The in vitro DPP-4 inhibitory activity was assessed using an assay kit. Additionally, an in silico study was conducted using molecular docking methods to analyze the occurring binding interactions. Results: The title compounds exhibited good inhibition against DPP-4 enzyme activity (IC Conclusions: A series of novel 2-({2-[(dialkylamino)methyl]quinazolin-4-one-3-yl}methyl)benzonitrile derivatives have been synthesized successfully. All the synthesized compounds had lower DPP-4 inhibitory activity than sitagliptin and the lead compound. The lower bioactivity was predicted due to the differences in the interaction between the synthesized and lead compounds against the DPP-4 enzyme.