2. Academic Validation
  3. Synthesis and structure-activity relationships for new 6-fluoroquinoline derivatives with antiplasmodial activity

Synthesis and structure-activity relationships for new 6-fluoroquinoline derivatives with antiplasmodial activity

  • Bioorg Med Chem. 2019 May 15;27(10):2052-2065. doi: 10.1016/j.bmc.2019.03.061.
Patrick Hochegger 1,  Johanna Faist 1,  Werner Seebacher 1,  Robert Saf 2,  Pascal Mäser 3,  Marcel Kaiser 3,  Robert Weis 4
Affiliations

Affiliations

  • 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; University of Basel, Petersplatz 1, 4003 Basel, Switzerland.
  • 4 Institute of Pharmaceutical Sciences, Pharmaceutical Chemistry, University of Graz, Schubertstraße 1, A-8010 Graz, Austria. Electronic address: robert.weis@uni-graz.at.
PMID: 30962114 DOI: 10.1016/j.bmc.2019.03.061
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; Plasmodium berghei; Plasmodium falciparum; Quinoline derivatives.

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