Abstract
The 3-hydroxypyran-4-one moiety (maltol) was incorporated into the structure of resveratrol to achieve a series of resveratrol-maltol hybrids (8a-8k) as novel multi-target-directed ligands (MTDLs). In vitro biological evaluation of the MTDLs revealed these compounds to have a triple function, namely inhibition of self-induced Aβ1-42 aggregation, antioxidation, and metal chelating activity. Among all the evaluated MTDLs, compounds 8i and 8j showed the most promise, demonstrating micromolar IC50 values for Aβ1-42 aggregation inhibition, more potent ABTS+ scavenging activity than Trolox, and good metal chelating activities.
Keywords:
3-Hydroxypyran-4-one; Alzheimer; Metal chelator; Resveratrol derivative; β-amyloid.
Copyright © 2018 Elsevier Ltd. All rights reserved.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Alzheimer Disease / drug therapy*
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Alzheimer Disease / metabolism
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Amyloid beta-Peptides / antagonists & inhibitors
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Amyloid beta-Peptides / metabolism
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Antioxidants / chemical synthesis
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Antioxidants / chemistry
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Antioxidants / pharmacology*
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Benzothiazoles / antagonists & inhibitors
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Chelating Agents / chemical synthesis
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Chelating Agents / chemistry
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Chelating Agents / pharmacology*
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Dose-Response Relationship, Drug
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Humans
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Ligands
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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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Peptide Fragments / antagonists & inhibitors
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Peptide Fragments / metabolism
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Protein Aggregates / drug effects
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Pyrones / chemistry
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Pyrones / pharmacology*
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Resveratrol / chemistry
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Resveratrol / pharmacology*
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Structure-Activity Relationship
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Sulfonic Acids / antagonists & inhibitors
Substances
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Amyloid beta-Peptides
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Antioxidants
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Benzothiazoles
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Chelating Agents
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Ligands
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Neuroprotective Agents
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Peptide Fragments
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Protein Aggregates
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Pyrones
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Sulfonic Acids
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amyloid beta-protein (1-42)
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2,2'-azino-di-(3-ethylbenzothiazoline)-6-sulfonic acid
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maltol
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Resveratrol