Discovery of 1-(phenylsulfonyl)-1H-indole-based multifunctional ligands targeting cholinesterases and 5-HT
Acetylcholinesterase
/ metabolism
Amyloid beta-Peptides
/ antagonists & inhibitors
Animals
Butyrylcholinesterase
/ metabolism
Cell Proliferation
/ drug effects
Cholinesterase Inhibitors
/ chemical synthesis
Dose-Response Relationship, Drug
Drug Discovery
Electrophorus
Hep G2 Cells
Horses
Humans
Indoles
/ chemical synthesis
Ligands
Mice
Microsomes, Liver
/ chemistry
Molecular Docking Simulation
Molecular Structure
Protein Aggregates
/ drug effects
Receptors, Serotonin
/ metabolism
Structure-Activity Relationship
tau Proteins
/ antagonists & inhibitors
5-HT(6) antagonists
Alzheimer's disease
Cholinesterase inhibitors
Multifunctional agents
Tau protein
β-amyloid
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:
05 Dec 2021
05 Dec 2021
Historique:
received:
09
06
2021
revised:
12
08
2021
accepted:
13
08
2021
pubmed:
31
8
2021
medline:
14
1
2022
entrez:
30
8
2021
Statut:
ppublish
Résumé
Multifunctional ligands as an essential variant of polypharmacology are promising candidates for the treatment of multi-factorial diseases like Alzheimer's disease. Based on clinical evidence and following the paradigm of multifunctional ligands we have rationally designed and synthesized a series of compounds targeting processes involved in the development of the disease. The biological evaluation led to the discovery of two compounds with favorable pharmacological characteristics and ADMET profile. Compounds 17 and 35 are 5-HT
Identifiants
pubmed: 34461507
pii: S0223-5234(21)00632-2
doi: 10.1016/j.ejmech.2021.113783
pii:
doi:
Substances chimiques
Amyloid beta-Peptides
0
Cholinesterase Inhibitors
0
Indoles
0
Ligands
0
Protein Aggregates
0
Receptors, Serotonin
0
serotonin 6 receptor
0
tau Proteins
0
indole
8724FJW4M5
Acetylcholinesterase
EC 3.1.1.7
Butyrylcholinesterase
EC 3.1.1.8
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
113783Informations de copyright
Copyright © 2021 The Authors. Published by 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.