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Design and synthesis of new piperidone grafted acetylcholinesterase inhibitors.
- Source :
-
Bioorganic & medicinal chemistry letters [Bioorg Med Chem Lett] 2017 Jan 15; Vol. 27 (2), pp. 228-231. Date of Electronic Publication: 2016 Nov 24. - Publication Year :
- 2017
-
Abstract
- Alzheimer's disease (AD) is a neurodegenerative disorder affecting 35million people worldwide. A common strategy to improve the well-being of AD patients consists on the inhibition of acetylcholinesterase with the concomitant increase of the neurotransmitter acetylcholine at cholinergic synapses. Two series of unreported N-benzylpiperidines 5(a-h) and thiazolopyrimidines 9(a-q) molecules were synthesized and evaluated in vitro for their acetylcholinesterase (AChE) inhibitory activities. Among the newly synthesized compounds, 5h, 9h, 9j, and 9p displayed higher AChE enzyme inhibitory activities than the standard drug, galantamine, with IC <subscript>50</subscript> values of 0.83, 0.98, and 0.73μM, respectively. Cytotoxicity studies of 5h, 9h, 9j, 9n and 9p on human neuroblastoma cells SH-SY5Y, showed no toxicity up to 40μM concentration. Molecular docking simulations of the active compounds 5h and 9p disclosed the crucial role of π-π-stacking in their binding interaction to the active site AChE enzyme. The presented compounds have potential as AChE inhibitors and potential AD drugs.<br /> (Copyright © 2016 Elsevier Ltd. All rights reserved.)
- Subjects :
- Alzheimer Disease metabolism
Cell Line, Tumor
Cholinesterase Inhibitors chemical synthesis
Cholinesterase Inhibitors chemistry
Dose-Response Relationship, Drug
Humans
Molecular Docking Simulation
Molecular Structure
Piperidones chemical synthesis
Piperidones chemistry
Structure-Activity Relationship
Acetylcholinesterase metabolism
Alzheimer Disease drug therapy
Cholinesterase Inhibitors pharmacology
Drug Design
Piperidones pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 1464-3405
- Volume :
- 27
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Bioorganic & medicinal chemistry letters
- Publication Type :
- Academic Journal
- Accession number :
- 27914796
- Full Text :
- https://doi.org/10.1016/j.bmcl.2016.11.065