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
Copyright policy )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
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.
Male, Guinea Pigs, Drug Evaluation, Preclinical, 610, Mice, Inbred Strains, [CHIM.THER]Chemical Sciences/Medicinal Chemistry, Alzheimer's Disease, Crystallography, X-Ray, Ligands, MTDL, Serotonin 5-HT4 Receptor Agonists, Structure-Activity Relationship, Piperidines, Alzheimer Disease, Animals, Humans, Computer Simulation, Molecular Targeted Therapy, Aniline Compounds, Donecopride, Mice, Inbred C57BL, Memory, Short-Term, Drug Design, Acetylcholinesterase, Cholinesterase Inhibitors, Receptors, Serotonin, 5-HT4, 5-HT4 Receptors
Male, Guinea Pigs, Drug Evaluation, Preclinical, 610, Mice, Inbred Strains, [CHIM.THER]Chemical Sciences/Medicinal Chemistry, Alzheimer's Disease, Crystallography, X-Ray, Ligands, MTDL, Serotonin 5-HT4 Receptor Agonists, Structure-Activity Relationship, Piperidines, Alzheimer Disease, Animals, Humans, Computer Simulation, Molecular Targeted Therapy, Aniline Compounds, Donecopride, Mice, Inbred C57BL, Memory, Short-Term, Drug Design, Acetylcholinesterase, Cholinesterase Inhibitors, Receptors, Serotonin, 5-HT4, 5-HT4 Receptors
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