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Screening Congo Red and its analogues for their ability to prevent the formation of PrP-res in scrapie-infected cells.
- Source :
-
The Journal of general virology [J Gen Virol] 2000 Apr; Vol. 81 (Pt 4), pp. 1155-64. - Publication Year :
- 2000
-
Abstract
- Transmissible spongiform encephalopathies (TSEs) are incurable, fatal diseases. The dye Congo Red (CR) can cure cells infected with agents of the sheep TSE, scrapie, but is not used as a therapeutic or prophylactic agent in vivo, as its effects are small, possibly due to low blood-brain barrier permeability, and complicated by its intrinsic carcinogenicity. In this paper, the development is described of a structure-activity profile for CR by testing a series of analogues of this dye for their ability to inhibit the formation of the protease-resistant prion protein, PrP-res, a molecular marker for the infectious agent, in the scrapie-infected, SMB cell line. It was found that the central benzidine unit in CR, which gives the molecule potential carcinogenicity, can be replaced by other, less toxic moieties and that the sulphonate groups on the core molecule can be replaced by carboxylic acids, which should improve the brain permeability of these compounds. However, detailed dose-response curves were generated for several derivatives and they revealed that, while some compounds showed inhibition of PrP-res accumulation at high concentrations, at low concentrations they actually stimulated levels of PrP-res above control values.
- Subjects :
- Animals
Coloring Agents therapeutic use
Congo Red therapeutic use
PrPSc Proteins biosynthesis
Scrapie metabolism
Sheep
Structure-Activity Relationship
Coloring Agents chemistry
Coloring Agents pharmacology
Congo Red chemistry
Congo Red pharmacology
PrPSc Proteins antagonists & inhibitors
Scrapie prevention & control
Subjects
Details
- Language :
- English
- ISSN :
- 0022-1317
- Volume :
- 81
- Issue :
- Pt 4
- Database :
- MEDLINE
- Journal :
- The Journal of general virology
- Publication Type :
- Academic Journal
- Accession number :
- 10725446
- Full Text :
- https://doi.org/10.1099/0022-1317-81-4-1155