Abstract
Lipoic acid (LA) is a natural antioxidant. Its structure was previously combined with that of the acetylcholinesterase inhibitor tacrine to give lipocrine (1), a lead compound multitargeted against Alzheimer's disease (AD). Herein, we further explore LA as a privileged structure for developing multimodal compounds to investigate AD. First, we studied the effect of LA chirality by evaluating the cholinesterase profile of 1's enantiomers. Then, a new series of LA hybrids was designed and synthesized by combining racemic LA with motifs of other known anticholinesterase agents (rivastigmine and memoquin). This afforded 4, which represents a step forward in the search for balanced anticholinesterase and antioxidant capacities.
Copyright © 2011 Elsevier Masson SAS. 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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Amyloid beta-Peptides / chemistry
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Antioxidants / chemical synthesis
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Antioxidants / chemistry
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Antioxidants / pharmacology
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Antioxidants / therapeutic use
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Butyrylcholinesterase / metabolism
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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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Cholinesterase Inhibitors / therapeutic use
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Drug Discovery / methods*
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Humans
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Ligands
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Peptide Fragments / chemistry
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Protein Multimerization / drug effects
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Protein Structure, Secondary
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Thioctic Acid / chemical synthesis
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Thioctic Acid / chemistry*
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Thioctic Acid / pharmacology*
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Thioctic Acid / therapeutic use
Substances
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Amyloid beta-Peptides
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Antioxidants
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Cholinesterase Inhibitors
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Ligands
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Peptide Fragments
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amyloid beta-protein (1-40)
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Thioctic Acid
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Acetylcholinesterase
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Butyrylcholinesterase