Abstract
A design strategy to convert a dual-binding site AChE inhibitor into triple functional compounds with promising in vitro profile against multifactorial syndromes, such as Alzheimer's disease, is proposed. The lead compound bis(7)-tacrine (2) was properly modified to confer to the new molecules the ability of chelating metals, involved in the neurodegenerative process. The multifunctional compounds show activity against human AChE, are able to inhibit the AChE-induced amyloid-beta aggregation, and chelate metals, such as iron and copper.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Acetylcholinesterase / chemistry*
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Alzheimer Disease / drug therapy*
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Amyloid beta-Peptides / chemistry*
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Binding Sites
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Butyrylcholinesterase / chemistry
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Chelating Agents / chemical synthesis
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Chelating Agents / chemistry
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Cholinesterase Inhibitors / chemical synthesis*
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Cholinesterase Inhibitors / chemistry
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Copper / chemistry
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Drug Design
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Ferric Compounds / chemistry
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Humans
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Ligands
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Models, Molecular
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Peptide Fragments / chemistry*
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Structure-Activity Relationship
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Tacrine / analogs & derivatives*
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Tacrine / chemical synthesis*
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Tacrine / chemistry
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Thermodynamics
Substances
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Amyloid beta-Peptides
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Chelating Agents
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Cholinesterase Inhibitors
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Ferric Compounds
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Ligands
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Peptide Fragments
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amyloid beta-protein (1-40)
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Tacrine
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Copper
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Acetylcholinesterase
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Butyrylcholinesterase
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cupric chloride