Inhibition of amyloid fibrillization of amyloid β peptide by 4,7-disubstituted coumarin derivatives
Language English Country Great Britain, England Media print-electronic
Document type Journal Article
PubMed
40680313
DOI
10.1016/j.bmc.2025.118302
PII: S0968-0896(25)00243-3
Knihovny.cz E-resources
- Keywords
- Alzheimer's disease, Amyloid aggregation, Antioxidant activity, Aβ peptide, Cell viability assay, Coumarin derivatives,
- MeSH
- Amyloid beta-Peptides * antagonists & inhibitors metabolism MeSH
- Antioxidants * pharmacology chemistry chemical synthesis MeSH
- Blood-Brain Barrier metabolism MeSH
- Coumarins * pharmacology chemistry chemical synthesis MeSH
- Humans MeSH
- Molecular Structure MeSH
- Cell Line, Tumor MeSH
- Peptide Fragments * metabolism antagonists & inhibitors MeSH
- Protein Aggregates drug effects MeSH
- Cell Survival drug effects MeSH
- Dose-Response Relationship, Drug MeSH
- Structure-Activity Relationship MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Names of Substances
- Amyloid beta-Peptides * MeSH
- Antioxidants * MeSH
- coumarin MeSH Browser
- Coumarins * MeSH
- Peptide Fragments * MeSH
- Protein Aggregates MeSH
Coumarins are well-known for their unique chemical structure and a wide range of biological effects. Various substituted coumarin-based compounds have emerged as promising candidates for the development of novel therapeutic agents against numerous diseases. This study was focused on the synthesis of new 4,7-disubstituted coumarin derivatives and investigation of their ability to inhibit the aggregation of Aβ40 peptide, their cytotoxic effect on SH-SY5Y cells, their antioxidant properties, and their ability to penetrate the blood-brain barrier (BBB). The results revealed that the trihydroxy derivatives 5a-c had been the most effective inhibitors of Aβ aggregation, promoting the formation of non-toxic, amorphous aggregates instead. Importantly, no significant decrease in the viability of SH-SY5Y neuroblastoma cells was observed after treatment with the studied coumarins. Among them, coumarin 5a demonstrated the strongest antioxidant activity, while compound 5b also exhibited good antioxidant properties, along with the best inhibition of Aβ aggregation (IC50 = 13.5 μM), and adequate permeability across the blood-brain barrier. These findings suggest that compound 5b is a promising candidate for further investigation in Alzheimer's disease pharmacotherapy.
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