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1,2-substituted 4-(1H)-quinolones: synthesis, antimalarial and antitrypanosomal activities in vitro. 2014

Abraham Wube, and Antje Hüfner, and Werner Seebacher, and Marcel Kaiser, and Reto Brun, and Rudolf Bauer, and Franz Bucar
Department of Pharmacognosy, Institute of Pharmaceutical Sciences, University of Graz, Universitätsplatz 4/1, A-8010 Graz, Austria. abraham.wube@uni-graz.at.

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.

UI MeSH Term Description Entries
D010963 Plasmodium falciparum A species of protozoa that is the causal agent of falciparum malaria (MALARIA, FALCIPARUM). It is most prevalent in the tropics and subtropics. Plasmodium falciparums,falciparums, Plasmodium
D002460 Cell Line Established cell cultures that have the potential to propagate indefinitely. Cell Lines,Line, Cell,Lines, Cell
D004353 Drug Evaluation, Preclinical Preclinical testing of drugs in experimental animals or in vitro for their biological and toxic effects and potential clinical applications. Drug Screening,Evaluation Studies, Drug, Pre-Clinical,Drug Evaluation Studies, Preclinical,Drug Evaluations, Preclinical,Evaluation Studies, Drug, Preclinical,Evaluation, Preclinical Drug,Evaluations, Preclinical Drug,Medicinal Plants Testing, Preclinical,Preclinical Drug Evaluation,Preclinical Drug Evaluations,Drug Screenings,Screening, Drug,Screenings, Drug
D000107 Acetylation Formation of an acetyl derivative. (Stedman, 25th ed) Acetylations
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D000962 Antimalarials Agents used in the treatment of malaria. They are usually classified on the basis of their action against plasmodia at different stages in their life cycle in the human. (From AMA, Drug Evaluations Annual, 1992, p1585) Anti-Malarial,Antimalarial,Antimalarial Agent,Antimalarial Drug,Anti-Malarials,Antimalarial Agents,Antimalarial Drugs,Agent, Antimalarial,Agents, Antimalarial,Anti Malarial,Anti Malarials,Drug, Antimalarial,Drugs, Antimalarial
D014344 Trypanocidal Agents Agents destructive to the protozoal organisms belonging to the suborder TRYPANOSOMATINA. Trypanocidal Drugs,Trypanocides,Trypanosomicidal Agents,Trypanosomicides,Agents, Trypanocidal,Agents, Trypanosomicidal,Drugs, Trypanocidal
D015363 Quinolones A group of derivatives of naphthyridine carboxylic acid, quinoline carboxylic acid, or NALIDIXIC ACID. Ketoquinoline,Ketoquinolines,Oxoquinoline,Oxoquinolines,Quinolinone,Quinolinones,Quinolone
D016833 Trypanosoma brucei rhodesiense A hemoflagellate subspecies of parasitic protozoa that causes Rhodesian sleeping sickness in humans. It is carried by Glossina pallidipes, G. morsitans and occasionally other species of game-attacking tsetse flies. Trypanosoma rhodesiense,Trypanosoma brucei rhodesienses,Trypanosoma rhodesienses,brucei rhodesiense, Trypanosoma,brucei rhodesienses, Trypanosoma,rhodesienses, Trypanosoma,rhodesienses, Trypanosoma brucei
D051381 Rats The common name for the genus Rattus. Rattus,Rats, Laboratory,Rats, Norway,Rattus norvegicus,Laboratory Rat,Laboratory Rats,Norway Rat,Norway Rats,Rat,Rat, Laboratory,Rat, Norway,norvegicus, Rattus

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