Similar Structure Activity Relationships of Quinoline Derivatives for antiprion and antimalarial effects - Archive ouverte HAL Accéder directement au contenu
Article Dans Une Revue Journal of Medicinal Chemistry Année : 2006

Similar Structure Activity Relationships of Quinoline Derivatives for antiprion and antimalarial effects

Résumé

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) of 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 sulphonamide quinoline derivatives, suggesting that some molecular targets of antiprion and antimalarial substances overlap.

Dates et versions

hal-00098660 , version 1 (25-09-2006)

Identifiants

Citer

Ralf Klingenstein, Patricia Melnyk, S. Rutger Leliveld, Adina Ryckebusch, Carsten Korth. Similar Structure Activity Relationships of Quinoline Derivatives for antiprion and antimalarial effects. Journal of Medicinal Chemistry, 2006, 49 (17), pp.5300-5308. ⟨10.1021/jm0602763⟩. ⟨hal-00098660⟩
247 Consultations
0 Téléchargements

Altmetric

Partager

Gmail Facebook X LinkedIn More