Tacrine Derivatives and Alzheimers Disease

Title: Tacrine Derivatives and Alzheimers Disease

Volume: 17 Issue: 17

Author(s): V. Tumiatti, A. Minarini, M.L. Bolognesi, A. Milelli, M. Rosini and C. Melchiorre

Affiliation:

Keywords: Neurodegenerative diseases, multi-target-directed ligands (MTDLs), dual binding acetylcholinesterase inhibitors, tacrine, tacrine homodimers, tacrine heterodimers, tacrine hybrids

Abstract: To date, the pharmacotherapy of Alzheimers disease (AD) has relied on acetylcholinesterase (AChE) inhibitors (AChEIs) and, more recently, an N-methyl-D-aspartate receptor (NMDAR) antagonist. AD is a multifactorial syndrome with several target proteins contributing to its etiology. “Multi-target-directed ligands” (MTDLs) have great potential for treating complex diseases such as AD because they can interact with multiple targets. The design of compounds that can hit more than one specific AD target thus represents an innovative strategy for AD treatment. Tacrine was the first AChEI introduced in therapy. Recent studies have demonstrated its ability to interact with different AD targets. Furthermore, numerous tacrine homo- and heterodimers have been developed with the aim of improving and enlarging its biological profile beyond its ability to act as an AChEI. Several tacrine hybrid derivatives have been designed and synthesized with the same goal. This review will focus on and summarize the last two years of research into the development of tacrine derivatives able to hit AD targets beyond simple AChE inhibition.

Cite this article as:

Tumiatti V., Minarini A., Bolognesi M.L., Milelli A., Rosini M. and Melchiorre C., Tacrine Derivatives and Alzheimers Disease, Current Medicinal Chemistry 2010; 17 (17) . https://dx.doi.org/10.2174/092986710791111206