PUBLICATION
Design, synthesis and evaluation of quinoline-O-carbamate derivatives as multifunctional agents for the treatment of Alzheimer's disease
- Authors
- Chen, H., Mi, J., Li, S., Liu, Z., Yang, J., Chen, R., Wang, Y., Ban, Y., Zhou, Y., Dong, W., Sang, Z.
- ID
- ZDB-PUB-230124-7
- Date
- 2023
- Source
- Journal of enzyme inhibition and medicinal chemistry 38: 21696822169682 (Journal)
- Registered Authors
- Dong, Wu
- Keywords
- Alzheimer’s disease, multifunctional agent, quinoline-O-carbamate derivatives, zebrafish AD model
- MeSH Terms
-
- Acetylcholinesterase/metabolism
- Alzheimer Disease*/drug therapy
- Amyloid beta-Peptides
- Animals
- Carbamates/pharmacology
- Cholinesterase Inhibitors/pharmacology
- Drug Design
- Hydroxyquinolines*
- Molecular Structure
- Neuroprotective Agents*
- Quinolines*/pharmacology
- Structure-Activity Relationship
- Zebrafish
- PubMed
- 36688444 Full text @ J Enzyme Inhib Med Chem
Citation
Chen, H., Mi, J., Li, S., Liu, Z., Yang, J., Chen, R., Wang, Y., Ban, Y., Zhou, Y., Dong, W., Sang, Z. (2023) Design, synthesis and evaluation of quinoline-O-carbamate derivatives as multifunctional agents for the treatment of Alzheimer's disease. Journal of enzyme inhibition and medicinal chemistry. 38:21696822169682.
Abstract
A series of novel quinoline-O-carbamate derivatives was rationally designed for treating Alzheimer's disease (AD) by multi-target-directed ligands (MTDLs) strategy. The target compounds were synthesised and evaluated by AChE/BuChE inhibition and anti-inflammatory property. The in vitro activities showed that compound 3f was a reversible dual eeAChE/eqBuChE inhibitor with IC50 values of 1.3 µM and 0.81 µM, respectively. Moreover, compound 3f displayed good anti-inflammatory property by decreasing the production of IL-6, IL-1β and NO. In addition, compound 3f presented significant neuroprotective effect on Aβ25-35-induced PC12 cell injury. Furthermore, compound 3f presented good stabilities in artificial gastrointestinal fluids, liver microsomes in vitro and plasma. Furthermore, compound 3f could improve AlCl3-induced zebrafish AD model by increasing the level of ACh. Therefore, compound 3f was a promising multifunctional agent for the treatment of AD.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping