Novel tacrine-tryptophan hybrids: Multi-target directed ligands as potential treatment for Alzheimer's disease.
Acetylcholinesterase
/ metabolism
Alzheimer Disease
/ drug therapy
Amyloid beta-Peptides
/ antagonists & inhibitors
Animals
Butyrylcholinesterase
/ metabolism
Cholinesterase Inhibitors
/ chemical synthesis
Dose-Response Relationship, Drug
Humans
Ligands
Male
Maze Learning
/ drug effects
Molecular Structure
Neuroprotective Agents
/ chemical synthesis
Protein Aggregates
/ drug effects
Rats
Rats, Wistar
Structure-Activity Relationship
Tacrine
/ chemistry
Tryptophan
/ chemistry
Acetylcholinesterase
Alzheimer's disease
Aβ42 self-aggregation
Blood-brain barrier
Multi-target directed ligands
Tacrine-tryptophan hybrids
X-ray crystallographic analysis
hAChEinduced Aβ40 aggregation
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 Apr 2019
15 Apr 2019
Historique:
received:
16
12
2018
revised:
07
02
2019
accepted:
07
02
2019
pubmed:
10
3
2019
medline:
23
4
2019
entrez:
10
3
2019
Statut:
ppublish
Résumé
A combination of tacrine and tryptophan led to the development of a new family of heterodimers as multi-target agents with potential to treat Alzheimer's disease. Based on the in vitro biological profile, compound S-K1035 was found to be the most potent inhibitor of human acetylcholinesterase (hAChE) and human butyrylcholinesterase (hBChE), demonstrating balanced IC
Identifiants
pubmed: 30851693
pii: S0223-5234(19)30135-7
doi: 10.1016/j.ejmech.2019.02.021
pii:
doi:
Substances chimiques
Amyloid beta-Peptides
0
Cholinesterase Inhibitors
0
Ligands
0
Neuroprotective Agents
0
Protein Aggregates
0
Tacrine
4VX7YNB537
Tryptophan
8DUH1N11BX
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
491-514Informations de copyright
Copyright © 2019 Elsevier Masson SAS. All rights reserved.