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Graveoline Analogs Exhibiting Selective Acetylcholinesterase Inhibitory Activity as Potential Lead Compounds for the Treatment of Alzheimer's Disease.
- Source :
-
Molecules (Basel, Switzerland) [Molecules] 2016 Jan 22; Vol. 21 (2), pp. 132. Date of Electronic Publication: 2016 Jan 22. - Publication Year :
- 2016
-
Abstract
- This study designed and synthesized a series of new graveoline analogs on the basis of the structural characteristics of acetylcholinesterase (AChE) dual-site inhibitors. The activity of these analogs was also evaluated. Results showed that the synthesized graveoline analogs displayed stronger inhibitory activity against AChE and higher selectivity than butyrylcholine esterase (BuChE) (Selectivity Index from 45 to 486). When the two sites in the graveoline parent ring substituting phenyl and amino terminal had six chemical bonds (n = 3) and the terminal amino was piperidine, compound 5c showed the best activity. Furthermore, the mechanism of action and binding mode were explored by enzyme kinetic simulation, molecular docking, and thioflavin T-based fluorometric assay. Cytotoxicity assay showed that the low concentration of the analogs did not affect the viability of the neurocyte SH-SY5Y.
- Subjects :
- Acetylcholinesterase chemistry
Alzheimer Disease drug therapy
Alzheimer Disease enzymology
Binding Sites
Butyrylcholinesterase metabolism
Cell Line
Cell Proliferation drug effects
Cholinesterase Inhibitors chemistry
Humans
Methoxsalen chemical synthesis
Methoxsalen chemistry
Methoxsalen pharmacology
Models, Molecular
Molecular Docking Simulation
Structure-Activity Relationship
Acetylcholinesterase metabolism
Cholinesterase Inhibitors chemical synthesis
Cholinesterase Inhibitors pharmacology
Methoxsalen analogs & derivatives
Subjects
Details
- Language :
- English
- ISSN :
- 1420-3049
- Volume :
- 21
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Molecules (Basel, Switzerland)
- Publication Type :
- Academic Journal
- Accession number :
- 26805806
- Full Text :
- https://doi.org/10.3390/molecules21020132