Novel Multitarget-Directed Ligands (MTDLs) with Acetylcholinesterase (AChE) Inhibitory and Serotonergic Subtype 4 Receptor (5-HT 4 R) Agonist Activities As Potential Agents against Alzheimer’s Disease: The Design of Donecopride

Cédric Lecoutey; Florence Gaven; Patrizia Giannoni; Katia Hamidouche; Damien Hedou; Emmanuelle Dubost; David Genest; Samir Yahiaoui; Thomas Freret; Valentine Bouet; François Dauphin; Jana Sopkova-de Oliveira Santos; Céline Ballandonne; Sophie Corvaisier; Aurélie Malzert-Fréon; Rémi Legay; Michel Boulouard; Sylvie Claeysen; Patrick Dallemagne

doi:10.1021/acs.jmedchem.5b00115

Back

Novel Multitarget-Directed Ligands (MTDLs) with Acetylcholinesterase (AChE) Inhibitory and Serotonergic Subtype 4 Receptor (5-HT 4 R) Agonist Activities As Potential Agents against Alzheimer’s Disease: The Design of Donecopride

Journal article

Open access

Peer reviewed

Novel Multitarget-Directed Ligands (MTDLs) with Acetylcholinesterase (AChE) Inhibitory and Serotonergic Subtype 4 Receptor (5-HT 4 R) Agonist Activities As Potential Agents against Alzheimer’s Disease: The Design of Donecopride

Cédric Lecoutey, Cédric Lecoutey, Florence Gaven, Patrizia Giannoni, Katia Hamidouche, Damien Hedou, Emmanuelle Dubost, David Genest, Samir Yahiaoui, Thomas Freret, …

Journal of Medicinal Chemistry, Vol.58(7), pp.3172-3187

30/03/2015

DOI: https://doi.org/10.1021/acs.jmedchem.5b00115

PMID: 25793650

Abstract

Alzheimer's Disease

Acetylcholinesterase

5-HT4 Receptors

Donecopride

MTDL

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 sAPPα release, accounting for a potential symptomatic and disease-modifying therapeutic benefit in the treatment of Alzheimer’s disease.

Files and links (1)

url

Find in HALView

Metrics

1 Record Views

Details

Title: Novel Multitarget-Directed Ligands (MTDLs) with Acetylcholinesterase (AChE) Inhibitory and Serotonergic Subtype 4 Receptor (5-HT 4 R) Agonist Activities As Potential Agents against Alzheimer’s Disease: The Design of Donecopride
Creators - without role: Cédric Lecoutey - Centre d'Etudes et de Recherche sur le Médicament de Normandie
Cédric Lecoutey - Centre d'Etudes et de Recherche sur le Médicament de Normandie
Florence Gaven - Université de Montpellier, Institut de Génomique Fonctionnelle - IGF
Patrizia Giannoni - Université de Montpellier, Institut de Génomique Fonctionnelle - IGF
Katia Hamidouche - Université de Caen Normandie
Damien Hedou - Université de Caen Normandie
Emmanuelle Dubost - Centre d'Etudes et de Recherche sur le Médicament de Normandie
David Genest - Centre d'Etudes et de Recherche sur le Médicament de Normandie
Samir Yahiaoui - Centre d'Etudes et de Recherche sur le Médicament de Normandie
Thomas Freret - Université de Caen Normandie
Valentine Bouet - Université de Caen Normandie
François Dauphin - Université de Caen Normandie
Jana Sopkova-de Oliveira Santos - Centre d'Etudes et de Recherche sur le Médicament de Normandie
Céline Ballandonne - Université de Caen Normandie
Sophie Corvaisier - Centre d'Etudes et de Recherche sur le Médicament de Normandie
Aurélie Malzert-Fréon - Centre d'Etudes et de Recherche sur le Médicament de Normandie
Rémi Legay - Université de Caen Normandie
Michel Boulouard - Université de Caen Normandie
Sylvie Claeysen - Université de Montpellier, Institut de Génomique Fonctionnelle - IGF
Patrick Dallemagne - Université de Caen Normandie
Publication Details: Journal of Medicinal Chemistry, Vol.58(7), pp.3172-3187
Grant note: This work was supported by funding from the Conseil Régional de Basse Normandie, France (Dispositif de Soutien aux Projets de Recherche Emergents), French Agence Nationale de la Recherche Projects MALAD ANR-12-JS007-0012-01 and ADAMGUARD ANR-12-BSV4-008-01, and Ligue Européenne Contre la Maladie d’Alzheimer Grant 12721.
Identifiers: 9937691009311
Academic Unit: Institut de Génomique Fonctionnelle - IGF
Language: English
Resource Type: Journal article
Local Fields: hal-02043873