Abstract
The search for novel and effective therapeutics for Alzheimer's disease (AD) is the main quest that remains to be resolved. The goal is to find a disease-modifying agent able to confront the multifactorial nature of the disease positively. Herewith, a family of huprineY-tryptophan heterodimers was prepared, resulting in inhibition of cholinesterase and neuronal nitric oxide synthase enzymes, with effect against amyloid-beta (Aβ) and potential ability to cross the blood-brain barrier. Their cholinesterase pattern of behavior was inspected using kinetic analysis in tandem with docking studies. These heterodimers exhibited a promising pharmacological profile with strong implication in AD.
Keywords:
Acetylcholinesterase; Alzheimer's disease; Amyloid-beta; Multi-target directed ligands; huprine Y; l-Tryptophan.
Copyright © 2021 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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Aminoquinolines / chemistry
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Aminoquinolines / pharmacology*
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Amyloid beta-Peptides / antagonists & inhibitors
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Amyloid beta-Peptides / 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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Dose-Response Relationship, Drug
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Heterocyclic Compounds, 4 or More Rings / chemistry
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Heterocyclic Compounds, 4 or More Rings / pharmacology*
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Humans
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Molecular Structure
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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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Structure-Activity Relationship
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Tryptophan / chemistry
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Tryptophan / pharmacology*
Substances
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Aminoquinolines
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Amyloid beta-Peptides
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Cholinesterase Inhibitors
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Heterocyclic Compounds, 4 or More Rings
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Neuroprotective Agents
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huprine Y
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Tryptophan
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Acetylcholinesterase