Design and synthesis of novel quinazolinone-1,2,3-triazole hybrids as new anti-diabetic agents: In vitro α-glucosidase inhibition, kinetic, and docking study

A novel series of quinazolinone-1,2,3-triazole hybrids 10a-p were designed, synthesized, and evaluated for their in vitro α-glucosidase inhibitory activity and all them exhibited α-glucosidase inhibitory activity more than standard drug acarbose. [Display omitted] •A novel series of quinazolinone-1,2,3-triazole hybrids 10a-p were synthesized as α-glucosidase inhibitors.•All compounds showed anti-α-glucosidase activity superior to acarbose.•Compound 10g was the most active compound that was around 6-fold more potent than acarbose.•Compound 10g was a competitive inhibitor for α-glucosidase with Ki value 117 µM.•Molecular docking study confirmed the results obtained through in vitro experiments. A novel series of quinazolinone-1,2,3-triazole hybrids 10a-p were designed, synthesized, and evaluated for their in vitro α-glucosidase inhibitory activity leading to efficient anti-diabetic agents. All synthesized compounds exhibited good inhibitory activity against yeast α-glucosidase (IC50 values in the range of 181.0–474.5 µM) even much more potent than standard drug acarbose (IC50 = 750.0). Among them, quinazolinone-1,2,3-triazoles possessing 4-bromobenzyl moiety connected to 1,2,3-triazole ring (10g and 10p) demonstrated the most potent inhibitory activity towards α-glucosidase. Compound 10g inhibited α-glucosidase in a competitive manner with Ki value of 117 µM. Furthermore, the binding modes of the most potent compounds 10g and 10p in the α-glucosidase active site was studied through in silico docking studies. Also, lack of cytotoxicity of compounds 10g and 10p was confirmed via MTT assay.