Synthesis and anti-prion activity evaluation of aminoquinoline analogues

Transmissible spongiform encephalopathies form a group of neurodegenerative diseases that affect humans and other mammals. They occur when the native prion protein is converted into an infectious isoform, the scrapie PrP, which aggregates, leading to neurodegeneration. Although several compounds wer...

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Bibliographic Details
Published in:European journal of medicinal chemistry 2010-11, Vol.45 (11), p.5468-5473
Main Authors: Macedo, Bruno, Kaschula, Catherine H., Hunter, Roger, Chaves, Juliana A.P., van der Merwe, Johannes D., Silva, Jerson L., Egan, Timothy J., Cordeiro, Yraima
Format: Article
Language:English
Subjects:
Aggregation
Aminoquinolines - chemical synthesis
Aminoquinolines - pharmacology
Antibiotics. Antiinfectious agents. Antiparasitic agents
Antimalarials
Antiparasitic agents
Antiviral Agents - chemical synthesis
Antiviral Agents - pharmacology
Biological and medical sciences
Drug Evaluation, Preclinical
Inhibitor
Magnetic Resonance Spectroscopy
Mass Spectrometry
Medical sciences
Neurodegeneration
Pharmacology. Drug treatments
Prion
Prions
Quinoline
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Summary:Transmissible spongiform encephalopathies form a group of neurodegenerative diseases that affect humans and other mammals. They occur when the native prion protein is converted into an infectious isoform, the scrapie PrP, which aggregates, leading to neurodegeneration. Although several compounds were evaluated for their ability to inhibit this conversion, there is no effective therapy for such diseases. Previous studies have shown that antimalarial compounds, such as quinolines, possess anti-scrapie activity. Here, we report the synthesis and evaluate the effect of aminoquinoline derivatives on the aggregation of a prion peptide. Our results show that 4-amino-7-chloroquinoline and N-(7-chloro-4-quinolinyl)-1,2-ethanediamine inhibit the aggregation significantly. Therefore, such aminoquinolines might be considered as candidates for the further development of therapeutics to prevent the development of prion diseases. The effect of 4-aminoquinolines on the aggregation of a prion peptide (PrP 109–149) was evaluated. 4-amino-7-chloroquinoline and N-(7-chloro-4-quinolinyl)-1,2-ethanediamine inhibit the aggregation and they might be potential lead compounds against prion diseases. [Display omitted]
ISSN:0223-5234
1768-3254
DOI:10.1016/j.ejmech.2010.07.054