RESUMEN

Based on the quantitative structure-activity relationship (QSAR), some novel p-aminobenzoic acid derivatives as promising cholinesterase enzyme inhibitors were designed, synthesized, characterized and evaluated to enhance learning and memory. The in vitro enzyme kinetic study of the synthesized compounds revealed the type of inhibition on the respective acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) enzymes. The in vivo studies of the synthesized compounds exhibited significant reversal of cognitive deficits in the animal models of amnesia as compared to standard drug donepezil. Further, the ex vivo studies in the specific brain regions like the hippocampus, hypothalamus, and prefrontal cortex regions also exhibited AChE inhibition comparable to standard donepezil. The in silico molecular docking and dynamics simulations studies of the most potent compound 22 revealed the consensual interactions at the active site pocket of the AChE.

Asunto(s)

Enfermedad de Alzheimer/tratamiento farmacológico , Inhibidores de la Colinesterasa/uso terapéutico , Nootrópicos/uso terapéutico , para-Aminobenzoatos/uso terapéutico , Acetilcolinesterasa/química , Acetilcolinesterasa/metabolismo , Animales , Encéfalo/metabolismo , Butirilcolinesterasa/química , Butirilcolinesterasa/metabolismo , Dominio Catalítico , Inhibidores de la Colinesterasa/síntesis química , Inhibidores de la Colinesterasa/química , Inhibidores de la Colinesterasa/toxicidad , Diseño de Fármacos , Femenino , Cinética , Masculino , Memoria/efectos de los fármacos , Simulación del Acoplamiento Molecular , Simulación de Dinámica Molecular , Estructura Molecular , Nootrópicos/síntesis química , Nootrópicos/química , Nootrópicos/toxicidad , Relación Estructura-Actividad Cuantitativa , Ratas , Semicarbazonas/síntesis química , Semicarbazonas/química , Semicarbazonas/uso terapéutico , Semicarbazonas/toxicidad , para-Aminobenzoatos/síntesis química , para-Aminobenzoatos/química , para-Aminobenzoatos/toxicidad