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

Abstract

Abstract 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 [IC 50 = 1.1 ± 0.15 μM], 3.5‐fold less‐hepatotoxic than tacrine at 1000 μM concentration, and consequently, a potential new hit‐compound for further investigation targeted to find a new agent for AD therapy.