RESUMEN

A series of 4-hydroxycoumarin-derived compounds 8a-p containing N-benzyl-1,2,3-triazole motif were designed as AChE inhibitors. The title compounds were obtained conveniently using multicomponent click reaction. The in vitro anticholinesterase evaluation of synthesized compounds against AChE and BuChE showed that some of them are potent and selective inhibitors of AChE. Among them, 2-chlorobenzyl derivative 8k showed the most potent activity against AChE (IC50  = 0.18 µm). Its activity was also superior to that of standard drug tacrine. The kinetic study and molecular docking simulation of the most potent compound 8k were also described.

Asunto(s)

4-Hidroxicumarinas/química , 4-Hidroxicumarinas/farmacología , Acetilcolinesterasa/metabolismo , Inhibidores de la Colinesterasa/química , Inhibidores de la Colinesterasa/farmacología , Triazoles/química , Triazoles/farmacología , 4-Hidroxicumarinas/síntesis química , Animales , Antagonistas Colinérgicos/síntesis química , Antagonistas Colinérgicos/química , Antagonistas Colinérgicos/farmacología , Inhibidores de la Colinesterasa/síntesis química , Química Clic , Diseño de Fármacos , Electrophorus , Cinética , Simulación del Acoplamiento Molecular , Triazoles/síntesis química