| Autor: |
Klingenstein, Ralf, Melnyk, Patricia, Rutger Leliveld, S., Ryckebusch, Adina, Korth, Carsten |
| Zdroj: |
Journal of Medicinal Chemistry; August 2006, Vol. 49 Issue: 17 p5300-5308, 9p |
| Abstrakt: |
Prion diseases are invariably fatal neurodegenerative diseases, in which the infectious agent consists of PrPSc, a pathogenic misfolded isoform of the normal cellular prion protein (PrPC). Until now, no pharmacological options exist for these novel pathogens. Here we describe the screening of a series of polyquinolines and quinolines linked to a large variety of terminal groups for their ability to cure a persistently prion infected cell line (ScN2a). Several compounds showed antiprion activity in the nanomolar range. The most active molecule, named 42, had a half-effective concentration (EC50) for antiprion activity of 50 nM. In a library of quinoline derivatives we were able to identify several structure−activity relationships (SAR). Remarkably, antiprion SAR in ScN2a cells were similar to antimalarial SAR in a cell model of malaria, particularly for the sulfonamide quinoline derivatives, suggesting that some molecular targets of antiprion and antimalarial substances overlap. |
| Databáze: |
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