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Aminoquinolones and Their Benzoquinone Dimer Hybrids as Modulators of Prion Protein Conversion
- Source :
- Molecules, Vol 27, Iss 22, p 7935 (2022)
- Publication Year :
- 2022
- Publisher :
- MDPI AG, 2022.
-
Abstract
- Prion Diseases or Transmissible Spongiform Encephalopathies are neurodegenerative conditions associated with a long incubation period and progressive clinical evolution, leading to death. Their pathogenesis is characterized by conformational changes of the cellular prion protein—PrPC—in its infectious isoform—PrPSc—which can form polymeric aggregates that precipitate in brain tissues. Currently, there are no effective treatments for these diseases. The 2,5-diamino-1,4-benzoquinone structure is associated with an anti-prion profile and, considering the biodynamic properties associated with 4-quinolones, in this work, 6-amino-4-quinolones derivatives and their respective benzoquinone dimeric hybrids were synthesized and had their bioactive profile evaluated through their ability to prevent prion conversion. Two hybrids, namely, 2,5-dichloro-3,6-bis((3-carboxy-1-pentyl-4-quinolone-6-yl)amino)-1,4-benzoquinone (8e) and 2,5-dichloro-3,6-bis((1-benzyl-3-carboxy-4-quinolone-6-yl)amino)-1,4-benzoquinone (8f), stood out for their prion conversion inhibition ability, affecting the fibrillation process in both the kinetics—with a shortening of the lag phase—and thermodynamics and their ability to inhibit the formation of protein aggregates without significant cytotoxicity at ten micromolar.
- Subjects :
- quinone
oxoquinoline
quinolone
scrapie
prion
Organic chemistry
QD241-441
Subjects
Details
- Language :
- English
- ISSN :
- 14203049
- Volume :
- 27
- Issue :
- 22
- Database :
- Directory of Open Access Journals
- Journal :
- Molecules
- Publication Type :
- Academic Journal
- Accession number :
- edsdoj.9ec09557c334c33bc36bc3e85a5b531
- Document Type :
- article
- Full Text :
- https://doi.org/10.3390/molecules27227935