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image of Design, Synthesis, Biological Evaluation and Docking Studies of 2-hydroxy-4-benzyloxy Chalcone Derivatives as Multifunctional Agents for the Treatment of Alzheimer's Disease

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.

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2025-01-09
2025-09-07

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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
Bentham Science Publishers ; https://doi.org/10.2174/0109298673328877241113091539
/content/journals/cmc/10.2174/0109298673328877241113091539
/content/journals/cmc/10.2174/0109298673328877241113091539
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  • Article Type:     Research Article
Keywords: anti-neuroinflammatory agents ; multifunctional anti-AD agents ; Aβ1-42 ; 2-hydroxy-4-benzyloxy chalcone derivatives ; Alzheimer's disease ; pathogenesis

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