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Synthesis and structure-activity relationships for new 6-fluoroquinoline derivatives with antiplasmodial activity
Patrick Hochegger1, Johanna Faist1, Werner Seebacher1
1Institute of Pharmaceutical Sciences, Pharmaceutical Chemistry, University of Graz, Schubertstraße 1, A-8010 Graz, Austria.
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).
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