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The discovery of new acetylcholinesterase inhibitors derived from pharmacophore modeling, virtual screening, docking simulation and bioassays.
- Source :
-
Molecular bioSystems [Mol Biosyst] 2016 Nov 15; Vol. 12 (12), pp. 3734-3742. - Publication Year :
- 2016
-
Abstract
- Hyperactivity of acetylcholinesterase (AChE) in the brain is the immediate cause of Alzheimer's disease (AD), which is one of the most prevalent fatal diseases afflicting numerous older people. In this research, an in silico study was carried out to find potential AChE inhibitors from a large chemical library. With clustering and lots of comprehensive analysis, some molecules were screened using in vitro bioassays. The IC <subscript>50</subscript> values against AChE ranged from 33.620 to 101.570 μM, while the inhibition ratios at 50 μM ranged from 11.37% to 77.35%. The binding mode between the inhibitor and the binding sites of AChE was studied. Four residues (Tyr133, Tyr124, Ser203 and Trp86) were suggested to be crucial because they can form hydrogen bonds with the ligand. Therefore, ZYQ1 and its derivatives might represent a promising starting point for the development of highly potent lead compounds for the treatment of AD.
- Subjects :
- Binding Sites
Biological Assay
Cluster Analysis
Computer Simulation
Drug Discovery methods
Hydrophobic and Hydrophilic Interactions
Inhibitory Concentration 50
Ligands
Molecular Conformation
Molecular Dynamics Simulation
Molecular Structure
Protein Binding
Workflow
Acetylcholinesterase chemistry
Acetylcholinesterase metabolism
Cholinesterase Inhibitors chemistry
Cholinesterase Inhibitors pharmacology
Molecular Docking Simulation
Subjects
Details
- Language :
- English
- ISSN :
- 1742-2051
- Volume :
- 12
- Issue :
- 12
- Database :
- MEDLINE
- Journal :
- Molecular bioSystems
- Publication Type :
- Academic Journal
- Accession number :
- 27801451
- Full Text :
- https://doi.org/10.1039/c6mb00661b