Novel Multitarget-Directed Ligands (MTDLs) with Acetylcholinesterase (AChE) Inhibitory and Serotonergic Subtype 4 Receptor (5-HT4R) Agonist Activities As Potential Agents against Alzheimer’s Disease: The Design of Donecopride
- 31 March 2015
- journal article
- research article
- Published by American Chemical Society (ACS) in Journal of Medicinal Chemistry
- Vol. 58 (7), 3172-3187
- https://doi.org/10.1021/acs.jmedchem.5b00115
Abstract
In this work, we describe the synthesis and in vitro evaluation of a novel series of multitarget-directed ligands (MTDL) displaying both nanomolar dual-binding site (DBS) acetylcholinesterase inhibitory effects and partial 5-HT4R agonist activity, among which donecopride was selected for further in vivo evaluations in mice. The latter displayed procognitive and antiamnesic effects and enhanced sAPPa release, accounting for a potential symptomatic and disease-modifying therapeutic benefit in the treatment of Alzheimers disease.Keywords
Funding Information
- Agence Nationale de la Recherche (ANR-12-BSV4-008-01, ANR-12-JS007-0012-01)
- Conseil Régional de Basse-Normandie
- Ligue Européenne Contre la Maladie d'Alzheimer (12721)
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