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Synthesis and structure-activity relationships for new 6-fluoroquinoline derivatives with antiplasmodial activity |
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| Authors: | Patrick Hochegger Johanna Faist Werner Seebacher Robert Saf Pascal Mäser Marcel Kaiser Robert Weis |
| Affiliation: | 1. Institute of Pharmaceutical Sciences, Pharmaceutical Chemistry, University of Graz, Schubertstraße 1, A-8010 Graz, Austria;2. Institute for Chemistry and Technology of Materials (ICTM), Graz University of Technology, Stremayrgasse 9, A-8010 Graz, Austria;3. Swiss Tropical and Public Health Institute, Socinstrasse 57, CH-4002 Basel, Switzerland;4. University of Basel, Petersplatz 1, 4003 Basel, Switzerland |
| Abstract: | The substitution of 6-fluoroquinolines was modified in ring positions 2 and 4. The new compounds were tested in vitro for their activities against a sensitive and a multidrug resistant strain of Plasmodium falciparum. Some physicochemical parametres were calculated (log P, log D, ligand efficiency) or determined experimentally (permeability). The most promising compounds were tested for their in vivo activity against Plasmodium berghei in a mouse model. The 6-fluoro-2-{4-[(4-methylpiperazin-1-yl)methyl]phenyl}-N-[2-(pyrrolidin-1-yl)ethyl]quinoline-4-carboxamide possessed proper physicochemical properties and showed high antiplasmodial activity in vitro (IC50?≤?0.0029?µM) and in vivo (99.6% activity). |
| Keywords: | Antimalarial Quinoline derivatives |
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