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Cholinesterase Inhibitors: Xanthostigmine Derivatives Blocking the Acetylcholinesterase-Induced β-Amyloid Aggregation
- Source :
- Journal of Medicinal Chemistry. 48:4444-4456
- Publication Year :
- 2005
- Publisher :
- American Chemical Society (ACS), 2005.
-
Abstract
- In continuing research that led us to identify a new class of carbamate derivatives acting as potent (Rampa et al. J. Med. Chem. 1998, 41, 3976) and long-lasting (Rampa et al. J. Med. Chem. 2001, 44, 3810) acetylcholinesterase (AChE) inhibitors, we obtained some analogues able to simultaneously block both the catalytic and the beta-amyloid (Abeta) proaggregatory activities of AChE. The key feature of these derivatives is a 2-arylidenebenzocycloalkanone moiety that provides the ability to bind at the AChE peripheral site responsible for promoting the Abeta aggregation. The new carbamates were tested in vitro for the inhibition of both cholinesterases and also for the ability to prevent the AChE-induced Abeta aggregation. All of the compounds had AChE IC(50) values in the nanomolar range and showed the ability to block the AChE-induced Abeta aggregation, thus supporting the feasibility of this new strategy in the search of compounds for the treatment of Alzheimer's disease.
- Subjects :
- Models, Molecular
Carbamate
Protein Conformation
Aché
medicine.medical_treatment
Structure-Activity Relationship
chemistry.chemical_compound
Drug Discovery
medicine
Moiety
Cholinesterase
chemistry.chemical_classification
Amyloid beta-Peptides
Binding Sites
Molecular Structure
biology
Chemistry
Acetylcholinesterase
language.human_language
In vitro
Kinetics
Enzyme
Biochemistry
Enzyme inhibitor
Butyrylcholinesterase
language
biology.protein
Molecular Medicine
Carbamates
Cholinesterase Inhibitors
Subjects
Details
- ISSN :
- 15204804 and 00222623
- Volume :
- 48
- Database :
- OpenAIRE
- Journal :
- Journal of Medicinal Chemistry
- Accession number :
- edsair.doi.dedup.....c6c20762b5f249603a52b76e19f41a6c