Multitarget-Directed Ligands: Innovative Chemical Probes and Therapeutic Tools Against Alzheimer's Disease

Maria      Laura Bolognesi; Elena      Simoni; Michela      Rosini; Anna      Minarini; Vincenzo      Tumiatti; Carlo      Melchiorre

doi:10.2174/156802611798184373

Abstract

Multitarget agents directed at selected molecular targets involved in the pathogenic cascade of Alzheimers disease (AD) have been increasingly sought after in recent years, with the aim of achieving enhanced therapeutic efficiency with respect to single-target drugs and drug candidates. At the same time, much attention has been devoted to identifying high quality pharmacological tools to help explore the molecular mechanisms underlying AD without being exposed to physicochemical challenges. Herein, we discuss several examples of both types of compounds, taken from our own research and derived from the leads memoquin, lipocrine and bis(7)tacrine.

Keywords: Neurodegenerative diseases, multifactorial diseases, multitarget-directed ligands (MTDLs), multifunctional compounds, memoquin, lipocrine, carbacrine, Alzheimer's disease(AD), enhanced therapeutic, potential culprits, preclinical models, multiple molecular abnormalities, neurodegenerative cascade, peripheral anionic site (PAS), benzoquinonemoiety