Synthesis, Biological Assessment and Molecular Modeling of Racemic QuinoPyranoTacrines for Alzheimer's Disease Therapy

摘要

In this report we describe the synthesis, biological evaluation and molecular modeling of new tacrine analogues such as QuinoPyranTacrines (QPTs), designed by juxtaposition of 1,4-naphthoquinone and tacrine. From these results we have identified QPT16 as a permeable, selective human acetylcholinesterase inhibitor IC50= 1.1 +/- 0.15 mu M, 3.5-fold less-hepatotoxic than tacrine at 1000 mu M concentration, and consequently, a potential new hit-compound for further investigation targeted to find a new agent for AD therapy.