Synthesis and anti-prion activity evaluation of aminoquinoline analogues
European Journal of Medicinal Chemistry
Faculdade de Farmácia, Universidade Federal Do Rio de Janeiro, Av Carlos Chagas Filho, Rio de Janeiro 21941-902, Brazil; Department of Chemistry, University of Cape Town, Rondebosch 7701, South Africa; Instituto de Bioquímica Médica, Universidade Federal Do Rio de Janeiro, Rio de Janeiro 21941-590, Brazil
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. © 2010 Elsevier Masson SAS. All rights reserved.
2 (7 chloro 4 quinolinyl) aminoethanol; 4 (cyclopentylamino) 7 chloro quinoline; 4 amino 7 chloroquinoline; 7 chloro 4 methylaminoquinoline; aminoquinoline derivative; n (7 chloro 4 quinolinyl) 1,2 ethanediamine; n 2 (7 chloro 4 quinolinyl) n 1,n 1 dimethyl 1,2 ethanediamine; n 2 (7 trifluoromethylthio 4 quinolinyl) n 1,n 1 diethyl 1,2 ethanediamine; prion protein; unclassified drug; animal experiment; anisotropy; article; clinical evaluation; drug synthesis; hamster; light scattering; nerve degeneration; nonhuman; protein aggregation; Aminoquinolines; Antiviral Agents; Drug Evaluation, Preclinical; Magnetic Resonance Spectroscopy; Mass Spectrometry; Prions