Abstract
A series of compounds containing an α,β-unsaturated carbonyl moiety, such as chalcones and coumarins were designed, synthesized and tested in a variety of assays to assess their potential as anti-Alzheimer's disease (AD) agents. The investigations included the inhibition of cholinesterases (AChE, BuChE), the inhibition of amyloid beta (Aβ) self-assembly and the disassembly of preformed Aβ oligomers. Several compounds showed excellent potential as multifunctional compounds for AD. Docking studies for 16 that performed well in all the assays gave a clear interpretation of various interactions in the gorge of AChE. Based on the results, the long-chain coumarin scaffold appears to be a promising structural template for further AD drug development.
Copyright © 2013 Elsevier Ltd. All rights reserved.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Acetylcholinesterase / chemistry
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Acetylcholinesterase / metabolism
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Alzheimer Disease / drug therapy
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Amyloid beta-Peptides / antagonists & inhibitors
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Amyloid beta-Peptides / metabolism
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Binding Sites
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Catalytic Domain
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Chalcones / chemical synthesis
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Chalcones / chemistry*
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Chalcones / therapeutic use
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Cholinesterase Inhibitors / chemical synthesis*
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Cholinesterase Inhibitors / chemistry
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Cholinesterase Inhibitors / therapeutic use
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Coumarins / chemical synthesis
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Coumarins / chemistry*
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Coumarins / therapeutic use
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Drug Design*
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Humans
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Molecular Docking Simulation
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Structure-Activity Relationship
Substances
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Amyloid beta-Peptides
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Chalcones
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Cholinesterase Inhibitors
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Coumarins
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coumarin
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Acetylcholinesterase