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Aminoquinolones and Their Benzoquinone Dimer Hybrids as Modulators of Prion Protein Conversion
- Source :
- Molecules; Volume 27; Issue 22; Pages: 7935
- Publication Year :
- 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 :
- Prions
Polymers
quinone
oxoquinoline
quinolone
scrapie
prion
Organic Chemistry
Pharmaceutical Science
Quinolones
Prion Proteins
Translocation, Genetic
Analytical Chemistry
Prion Diseases
Chemistry (miscellaneous)
Drug Discovery
Benzoquinones
Molecular Medicine
Humans
Physical and Theoretical Chemistry
Subjects
Details
- ISSN :
- 14203049
- Volume :
- 27
- Issue :
- 22
- Database :
- OpenAIRE
- Journal :
- Molecules (Basel, Switzerland)
- Accession number :
- edsair.doi.dedup.....850dfbf245290852eec1b6a295dbc2d9