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2000
Volume 33, Issue 2
  • ISSN: 0929-8673
  • E-ISSN: 1875-533X

Abstract

Background

Alzheimer's disease (AD) is the most prevalent neurodegenerative disorder, but no drugs can cure this disease. Chalcones possess good antioxidant activity, anti-neuroinflammatory activity, neuroprotective effects, inhibitory effects on A aggregation, and A disaggregation ability. Therefore, chalcones are ideal lead compounds, and the discovery of novel anti-AD agent-based chalcones is necessary.

Methods

Hydroxy groups and aryl benzyl ether groups were introduced into chalcone scaffolds to obtain a series of 2-hydroxyl-4-benzyloxy chalcone derivatives. These derivatives were further synthesized, biologically evaluated, and docked.

Results

Most target derivatives exhibited good anti-AD activities. In particular, compound had excellent inhibitory effects on self-induced A aggregation (90.8% inhibition rate at 25 μM) and Cu2+ induced A aggregation (93.4% inhibition rate at 25 μM). In addition, it also exhibited good A fibril disaggregation ability (64.7% at 25 μM), significant antioxidative activity (ORAC = 2.03 Trolox equivalent), moderate MAO-B inhibition (IC = 4.81 μM), selective metal chelation, appropriate BBB permeation, and dramatic anti-neuroinflammatory ability. In addition, compound relieved AD symptoms and protected hippocampal neurons .

Conclusion

Compound is a promising multifunctional anti-A agent.

© 2026 Bentham Science Publishers
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Design, Synthesis, Biological Evaluation and Docking Studies of 2-hydroxy-4-benzyloxy Chalcone Derivatives as Multifunctional Agents for the Treatment of Alzheimer's Disease
Curr. Med. Chem. 33, 351 (2026); https://doi.org/10.2174/0109298673328877241113091539
/content/journals/cmc/10.2174/0109298673328877241113091539
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  • Article Type:     Research Article
Keyword(s): 2-hydroxy-4-benzyloxy chalcone derivatives; Alzheimer's disease; anti-neuroinflammatory agents; Aβ1-42; multifunctional anti-AD agents; pathogenesis

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