title: 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.affiliation: Faculdade de Farmácia, Universidade Federal do Rio de Janeiro, Av Carlos Chagas Filho, Rio de Janeiro 21941-902, Brazil.
authors.forename: Bruno
authors.initials: B
authors.lastname: Macedo
authors.forename: Catherine H
authors.initials: CH
authors.lastname: Kaschula
authors.forename: Roger
authors.initials: R
authors.lastname: Hunter
authors.forename: Juliana A P
authors.initials: JA
authors.lastname: Chaves
authors.forename: Johannes D
authors.initials: JD
authors.lastname: van der Merwe
authors.forename: Jerson L
authors.initials: JL
authors.lastname: Silva
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: Egan
authors.forename: Yraima
authors.initials: Y
authors.lastname: Cordeiro
mesh_terms: D000634:Aminoquinolines / Q000138:chemical synthesis* / Q000494:pharmacology*; D000998:Antiviral Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D004353:Drug Evaluation, Preclinical; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D011328:Prions
chemical_list: D000634:Aminoquinolines; D000998:Antiviral Agents; D011328:Prions