Novel drug-like fluorenyl derivatives as selective butyrylcholinesterase and β-amyloid inhibitors for the treatment of Alzheimer's disease.
Humans
Butyrylcholinesterase
/ metabolism
Amyloid beta-Peptides
/ metabolism
Alzheimer Disease
/ drug therapy
Cholinesterase Inhibitors
/ pharmacology
Structure-Activity Relationship
Molecular Dynamics Simulation
Acetylcholinesterase
/ metabolism
Drug Design
Molecular Structure
Molecular Docking Simulation
Aggregation
Alzheimer’s disease
Butyrylcholinesterase inhibitors
Drug-likeness
Fluorene scaffold
β-amyloid
Journal
Bioorganic & medicinal chemistry
ISSN: 1464-3391
Titre abrégé: Bioorg Med Chem
Pays: England
ID NLM: 9413298
Informations de publication
Date de publication:
06 06 2023
06 06 2023
Historique:
received:
06
04
2023
revised:
23
04
2023
accepted:
12
05
2023
medline:
2
6
2023
pubmed:
27
5
2023
entrez:
26
5
2023
Statut:
ppublish
Résumé
Butyrylcholinesterase (BuChE) and amyloid β (Aβ) aggregation remain important biological target and mechanism in the search for effective treatment of Alzheimer's disease. Simultaneous inhibition thereof by the application of multifunctional agents may lead to improvement in terms of symptoms and causes of the disease. Here, we present the rational design, synthesis, biological evaluation and molecular modelling studies of novel series of fluorene-based BuChE and Aβ inhibitors with drug-like characteristics and advantageous Central Nervous System Multiparameter Optimization scores. Among 17 synthesized and tested compounds, we identified 22 as the most potent eqBuChE inhibitor with IC
Identifiants
pubmed: 37236021
pii: S0968-0896(23)00181-5
doi: 10.1016/j.bmc.2023.117333
pii:
doi:
Substances chimiques
Butyrylcholinesterase
EC 3.1.1.8
Amyloid beta-Peptides
0
Cholinesterase Inhibitors
0
Acetylcholinesterase
EC 3.1.1.7
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
117333Informations de copyright
Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Anna Pasieka reports financial support was provided by National Science Center Poland.