Similar Structure−Activity Relationships of Quinoline Derivatives for Antiprion and Antimalarial Effects
Identifieur interne : 000333 ( France/Analysis ); précédent : 000332; suivant : 000334Similar Structure−Activity Relationships of Quinoline Derivatives for Antiprion and Antimalarial Effects
Auteurs : Ralf Klingenstein [France] ; Patricia Melnyk [France] ; S. Rutger Leliveld [France] ; Adina Ryckebusch [France] ; Carsten Korth [France, Allemagne]Source :
- Journal of Medicinal Chemistry [ 0022-2623 ] ; 2006.
Abstract
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.
Url:
DOI: 10.1021/jm0602763
Affiliations:
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ISTEX:5EFE8F7BFB49F223533A60B276110A273E50F8C3Le document en format XML
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Med. Chem.</title><idno type="ISSN">0022-2623</idno><idno type="eISSN">1520-4804</idno><imprint><publisher>American Chemical Society</publisher><date type="e-published" when="2006-08-02">2006</date><date when="2006-08-24">2006</date><biblScope unit="vol">49</biblScope><biblScope unit="issue">17</biblScope><biblScope unit="page" from="5300">5300</biblScope><biblScope unit="page" to="5308">5308</biblScope></imprint><idno type="ISSN">0022-2623</idno></series></biblStruct></sourceDesc><seriesStmt><idno type="ISSN">0022-2623</idno></seriesStmt></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract">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. 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