Back to Search
Start Over
Evaluation of the antiprion activity of 6-aminophenanthridines and related heterocycles
- Source :
- European Journal of Medicinal Chemistry, European Journal of Medicinal Chemistry, Elsevier, 2014, 82, pp.363-371. ⟨10.1016/j.ejmech.2014.05.083⟩, European Journal of Medicinal Chemistry, 2014, 82, pp.363-371. ⟨10.1016/j.ejmech.2014.05.083⟩
- Publication Year :
- 2014
- Publisher :
- Elsevier BV, 2014.
-
Abstract
- International audience; Series of 6-aminophenanthridines and related heterocyclic compounds such as benzonaphtyridines were prepared. Reduction of one of the three aromatic rings was also performed. The compounds were first tested for their antiprion activity in a previously described yeast-based colourimetric prion assay. The most potent derivatives were then assayed ex vivo against the mammalian prion PrP(Sc) in a cell-based assay. Several of the new compounds were found more potent than the parent lead 6-aminophenanthridine. The most promising compounds against yeast and mammalian prions were 8-azido-6-aminophenanthridine (3m), and 7,10-dihydrophenanthridin-6-amine (14). In the mammalian cell-based assay, the IC50 of these two compounds were around 5 μM and 1.8 μM, respectively.
- Subjects :
- Models, Molecular
MESH: Heterocyclic Compounds
[SDV.BBM.BS] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Structural Biology [q-bio.BM]
Prions
MESH: Mice, Transgenic
MESH: Molecular Structure
Cell
Mice, Transgenic
Saccharomyces cerevisiae
Mice
Structure-Activity Relationship
03 medical and health sciences
chemistry.chemical_compound
MESH: Prions
MESH: Structure-Activity Relationship
0302 clinical medicine
Heterocyclic Compounds
Mammalian cell
Drug Discovery
medicine
Animals
MESH: Animals
MESH: Mice
IC50
Phenanthridine
030304 developmental biology
Pharmacology
0303 health sciences
Molecular Structure
[SDV.BBM.BS]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Structural Biology [q-bio.BM]
Neurodegenerative diseases
Organic Chemistry
Aromaticity
General Medicine
MESH: Phenanthridines
MESH: Saccharomyces cerevisiae
Yeast
Phenanthridines
3. Good health
[SDV.BBM.BS]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biomolecules [q-bio.BM]
medicine.anatomical_structure
chemistry
Biochemistry
Protein folding
MESH: Models, Molecular
030217 neurology & neurosurgery
Ex vivo
Protein misfolding
Subjects
Details
- ISSN :
- 02235234 and 17683254
- Volume :
- 82
- Database :
- OpenAIRE
- Journal :
- European Journal of Medicinal Chemistry
- Accession number :
- edsair.doi.dedup.....4d34d10c622c66942b170506185c079f