title: 1,2-substituted 4-(1H)-quinolones: synthesis, antimalarial and antitrypanosomal activities in vitro.
abstract: A diverse array of 4-(1H)-quinolone derivatives bearing substituents at positions 1 and 2 were synthesized and evaluated for antiprotozoal activities against Plasmodium falciparum and Trypanosoma brucei rhodesiense, and cytotoxicity against L-6 cells in vitro. Furthermore, selectivity indices were also determined for both parasites. All compounds tested showed antimalarial activity at low micromolar concentrations, with varied degrees of selectivity against L-6 cells. Compound 5a was found to be the most active against P. falciparum, with an IC50 value of 90 nM and good selectivity for the malarial parasite compared to the L-6 cells. Compound 10a, on the other hand, showed a strong antitrypanosomal effect with an IC50 value of 1.25 µM. In this study side chain diversity was explored by varying the side chain length and substitution pattern on the aliphatic group at position-2 and a structure-antiprotozoal activity study revealed that the aromatic ring introduced at C-2 contributed significantly to the antiprotozoal activities.
authors.affiliation: Department of Pharmacognosy, Institute of Pharmaceutical Sciences, University of Graz, Universitätsplatz 4/1, A-8010 Graz, Austria. abraham.wube@uni-graz.at.
authors.forename: Abraham
authors.initials: A
authors.lastname: Wube
authors.affiliation: Department of Pharmaceutical Chemistry, Institute of Pharmaceutical Sciences, University of Graz, Universitätsplatz 1, A-8010 Graz, Austria. antje.huefner@uni-graz.at.
authors.forename: Antje
authors.initials: A
authors.lastname: Hüfner
authors.affiliation: Department of Pharmaceutical Chemistry, Institute of Pharmaceutical Sciences, University of Graz, Universitätsplatz 1, A-8010 Graz, Austria. we.seebacher@uni-graz.at.
authors.forename: Werner
authors.initials: W
authors.lastname: Seebacher
authors.affiliation: Swiss Tropical and Public Health Institute, Socinstrasse 57, CH-4002 Basel, Switzerland. Marcel.Kaiser@unibas.ch.
authors.forename: Marcel
authors.initials: M
authors.lastname: Kaiser
authors.affiliation: Swiss Tropical and Public Health Institute, Socinstrasse 57, CH-4002 Basel, Switzerland. reto.brun@unibas.ch.
authors.forename: Reto
authors.initials: R
authors.lastname: Brun
authors.affiliation: Department of Pharmacognosy, Institute of Pharmaceutical Sciences, University of Graz, Universitätsplatz 4/1, A-8010 Graz, Austria. rudolf.bauer@uni-graz.at.
authors.forename: Rudolf
authors.initials: R
authors.lastname: Bauer
authors.affiliation: Department of Pharmacognosy, Institute of Pharmaceutical Sciences, University of Graz, Universitätsplatz 4/1, A-8010 Graz, Austria. franz.bucar@uni-graz.at.
authors.forename: Franz
authors.initials: F
authors.lastname: Bucar
mesh_terms: D000107:Acetylation; D000818:Animals; D000962:Antimalarials / Q000138:chemical synthesis / Q000494:pharmacology*; D002460:Cell Line; D004353:Drug Evaluation, Preclinical; D020128:Inhibitory Concentration 50; D021261:Parasitic Sensitivity Tests; D010963:Plasmodium falciparum / Q000187:drug effects; D015363:Quinolones / Q000138:chemical synthesis / Q000494:pharmacology*; D051381:Rats; D014344:Trypanocidal Agents / Q000138:chemical synthesis / Q000494:pharmacology*; D016833:Trypanosoma brucei rhodesiense / Q000187:drug effects
chemical_list: D000962:Antimalarials; D015363:Quinolones; D014344:Trypanocidal Agents