Synthesis and anti-prion activity evaluation of aminoquinoline analogues.

Abstract

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.

• Authors: Bruno Macedo, Catherine H Kaschula, Roger Hunter, Juliana A P Chaves, Johannes D van der Merwe, Jerson L Silva, Timothy J Egan, Yraima Cordeiro
• Journal: European journal of medicinal chemistry (Eur J Med Chem) Vol. 45 Issue 11 Pg. 5468-73 (Nov 2010) ISSN: 1768-3254 [Electronic] France
• PMID: 20797807 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2010 Elsevier Masson SAS. All rights reserved.

Chemical References

• Aminoquinolines
• Antiviral Agents
• Prions

Topics

• Aminoquinolines (chemical synthesis, pharmacology)
• Antiviral Agents (chemical synthesis, pharmacology)
• Drug Evaluation, Preclinical
• Magnetic Resonance Spectroscopy
• Mass Spectrometry
• Prions