Abstract
A series of berberine-phenyl-benzoheterocyclic (26-29) and tacrine-phenyl-benzoheterocyclic hybrids (44-46) were synthesised and evaluated as multifunctional anti-Alzheimer's disease agents. Compound 44b, tacrine linked with phenyl-benzothiazole by 3-carbon spacers, was the most potent AChE inhibitor with an IC(50) value of 0.017 μM. This compound demonstrated similar Aβ aggregation inhibitory activity with cucurmin (51.8% vs 52.1% at 20 μM, respectively), indicating that this hybrid is an excellent multifunctional drug candidate for AD.
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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Amyloid beta-Peptides / antagonists & inhibitors*
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Amyloid beta-Peptides / metabolism
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Berberine / chemistry*
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Binding Sites
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Butyrylcholinesterase / metabolism
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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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Cholinesterases / chemistry
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Cholinesterases / metabolism*
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Enzyme Activation / drug effects
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Heterocyclic Compounds / chemistry*
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Heterocyclic Compounds / pharmacology
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Humans
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Kinetics
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Molecular Dynamics Simulation
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Protein Structure, Tertiary
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Tacrine / chemistry*
Substances
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Amyloid beta-Peptides
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Cholinesterase Inhibitors
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Heterocyclic Compounds
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Berberine
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Tacrine
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Acetylcholinesterase
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Butyrylcholinesterase
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Cholinesterases