Abstract
We have identified tryptophan-based selective nanomolar butyrylcholinesterase (BChE) inhibitors. They are defined according to their chemical modularity, novel binding mode revealed by five solved crystal structures with human BChE, low cytotoxicity, and predicted permeability of the blood-brain barrier. Altogether, these factors indicate their potential as unique lead compounds for symptomatic therapy against Alzheimer's disease.
MeSH terms
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Alzheimer Disease / drug therapy*
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Alzheimer Disease / metabolism
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Butyrylcholinesterase / metabolism*
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Cell Line, Tumor
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Cell Survival / drug effects
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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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Crystallography, X-Ray
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Dose-Response Relationship, Drug
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Humans
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Models, Molecular
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Molecular Structure
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Structure-Activity Relationship
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Tryptophan / chemistry*
Substances
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Cholinesterase Inhibitors
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Tryptophan
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Butyrylcholinesterase