RESUMEN

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.

Asunto(s)

Antineoplásicos/farmacología , Inhibidores de Glicósido Hidrolasas/farmacología , Hipoglucemiantes/farmacología , Simulación del Acoplamiento Molecular , Quinazolinonas/farmacología , Triazoles/farmacología , alfa-Glucosidasas/metabolismo , Antineoplásicos/síntesis química , Antineoplásicos/química , Proliferación Celular/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Diseño de Fármacos , Ensayos de Selección de Medicamentos Antitumorales , Inhibidores de Glicósido Hidrolasas/síntesis química , Inhibidores de Glicósido Hidrolasas/química , Humanos , Hipoglucemiantes/síntesis química , Hipoglucemiantes/química , Cinética , Células MCF-7 , Estructura Molecular , Quinazolinonas/síntesis química , Quinazolinonas/química , Relación Estructura-Actividad , Triazoles/síntesis química , Triazoles/química