Synthesis, in vitro evaluation and molecular docking of a new class of indolylpropyl benzamidopiperazines as dual AChE and SERT ligands for Alzheimer's disease.
Acetylcholinesterase
/ metabolism
Alzheimer Disease
/ drug therapy
Amyloid beta-Peptides
/ metabolism
Animals
Antidepressive Agents
/ chemical synthesis
Cell Line
Cholinesterase Inhibitors
/ chemical synthesis
Donepezil
/ chemistry
Drug Design
Humans
Mice
Molecular Docking Simulation
Neuroblastoma
Piperazines
/ chemical synthesis
Protein Conformation
Serotonin Plasma Membrane Transport Proteins
/ metabolism
Selective Serotonin Reuptake Inhibitors
/ chemical synthesis
Structure-Activity Relationship
AChE
Alzheimer’s disease
Dual-active compounds
Indole derivatives
Multitarget
SERT
Journal
European journal of medicinal chemistry
ISSN: 1768-3254
Titre abrégé: Eur J Med Chem
Pays: France
ID NLM: 0420510
Informations de publication
Date de publication:
15 Jul 2020
15 Jul 2020
Historique:
received:
13
01
2020
revised:
11
04
2020
accepted:
20
04
2020
pubmed:
11
5
2020
medline:
27
1
2021
entrez:
11
5
2020
Statut:
ppublish
Résumé
During the last decade, the one drug-one target strategy has resulted to be inefficient in facing diseases with complex ethiology like Alzheimer's disease and many others. In this context, the multitarget paradigm has emerged as a promising strategy. Based on this consideration, we aim to develop novel molecules as promiscuous ligands acting in two or more targets at the same time. For such purpose, a new series of indolylpropyl-piperazinyl oxoethyl-benzamido piperazines were synthesized and evaluated as multitarget-directed drugs for the serotonin transporter (SERT) and acetylcholinesterase (AChE). The ability to decrease β-amyloid levels as well as cell toxicity of all compounds were also measured. In vitro results showed that at least four compounds displayed promising activity against SERT and AChE. Compounds 18 and 19 (IC
Identifiants
pubmed: 32388114
pii: S0223-5234(20)30338-X
doi: 10.1016/j.ejmech.2020.112368
pii:
doi:
Substances chimiques
Amyloid beta-Peptides
0
Antidepressive Agents
0
Cholinesterase Inhibitors
0
Piperazines
0
Serotonin Plasma Membrane Transport Proteins
0
Serotonin Uptake Inhibitors
0
Donepezil
8SSC91326P
Acetylcholinesterase
EC 3.1.1.7
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
112368Informations de copyright
Copyright © 2020 Elsevier Masson SAS. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.