Abstract
A novel series of tacrine-caffeic acid hybrids (5a-f) were designed and synthesized by combining caffeic acid (CA) with tacrine. The antioxidant study revealed that all the hybrids have much more antioxidant capacities compared to CA. Among these compounds, 5e showed the highest selectivity in inhibiting acetylcholinesterase (AChE) over butyrylcholinesterase (BuChE). Enzyme kinetic study had suggested that 5e binds to both catalytic (CAS) and peripheral anionic sites (PAS) of AChE. Moreover, compound 5e also inhibited self- or AChE-induced β-amyloid(1-40) aggregation, as well as had potent neuroprotective effects against H(2)O(2)- and glutamate- induced cell death with low toxicity in HT22 cells.
Copyright © 2012 Elsevier Ltd. All rights reserved.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Acetylcholinesterase / metabolism
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Alzheimer Disease / drug therapy*
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Alzheimer Disease / metabolism
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Amyloid beta-Peptides / antagonists & inhibitors*
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Amyloid beta-Peptides / metabolism
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Animals
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Antioxidants / chemical synthesis
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Antioxidants / chemistry
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Antioxidants / pharmacology
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Butyrylcholinesterase / metabolism
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Caffeic Acids / chemical synthesis
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Caffeic Acids / chemistry*
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Caffeic Acids / pharmacology*
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Cell Death / drug effects
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Cell Line
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Cholinesterase Inhibitors / chemical synthesis
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Cholinesterase Inhibitors / chemistry
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Cholinesterase Inhibitors / pharmacology
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Drug Design
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Hydrogen Peroxide / metabolism
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Mice
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Neurons / drug effects
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Neurons / metabolism
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Neuroprotective Agents / chemical synthesis
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Neuroprotective Agents / chemistry
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Neuroprotective Agents / pharmacology
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Tacrine / chemical synthesis
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Tacrine / chemistry*
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Tacrine / pharmacology*
Substances
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Amyloid beta-Peptides
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Antioxidants
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Caffeic Acids
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Cholinesterase Inhibitors
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Neuroprotective Agents
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Tacrine
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Hydrogen Peroxide
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Acetylcholinesterase
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Butyrylcholinesterase
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caffeic acid