RESUMEN
Synthesis and anticholinesterase activity of 18 previously unpublished indole- and tryptophan-derived compounds are disclosed. These sp3-rich compounds containing an indole structural unit exhibit selective submicromolar inhibition of human butyrylcholinesterase (hBChE). The structures of the newly synthesized compounds were confirmed by 1H and 13C NMR, IR spectroscopy, and high-resolution mass spectrometry.
Asunto(s)
Butirilcolinesterasa , Inhibidores de la Colinesterasa , Humanos , Butirilcolinesterasa/química , Inhibidores de la Colinesterasa/farmacología , Indoles/farmacología , Indoles/química , Acetilcolinesterasa/metabolismo , Relación Estructura-Actividad , Simulación del Acoplamiento MolecularRESUMEN
We have identified tryptophan-based selective nanomolar butyrylcholinesterase (BChE) inhibitors. They are defined according to their chemical modularity, novel binding mode revealed by five solved crystal structures with human BChE, low cytotoxicity, and predicted permeability of the blood-brain barrier. Altogether, these factors indicate their potential as unique lead compounds for symptomatic therapy against Alzheimer's disease.