In vitro antimalarial activity of novel trifluoromethyl- and bis(trifluoromethyl)quinoline derivatives.
The in vitro antimalarial activity of a series of 2- and 8-trifluoromethyl- and 2,8-bis(trifluoromethyl)quinoline-4-(5-pyrimidino) and N4-ethyl-5-nitroimidazolo)methylene ketones was assessed against the chloroquine-sensitive strain (D10) of Plasmodium falciparum. Although the in vitro antimalarial activity of these compounds is more or less of the same order of magnitude, derivatives containing two trifluoromethyl groups achieve a slightly higher in vitro activity than compounds with one trifluoromethyl group, with 2,8-bis(trifluoromethyl) quinoline-4-(N4-ethyl-5-nitroimidazolo) methylene and 2,8-bis(trifluoromethyl) quinoline-4-(5-pyrimidino) ketones showing IC50 of 4.8 and 5.2 micrograms/ml, respectively. These compounds seem to bind to DNA by intercalation.
Department of Pharmaceutical Chemistry, University of the North, Sovenga, Republic of South Africa. kgokongj@unin.unorth.ac.za
J L
JL
Kgokong
G M
GM
Matsabisa
J C
JC
Breytenbach
D000818:Animals; D000962:Antimalarials / Q000494:pharmacology*; D001667:Binding, Competitive / Q000187:drug effects; D002738:Chloroquine / Q000494:pharmacology; D004247:DNA / Q000187:drug effects / Q000378:metabolism; D004996:Ethidium / Q000378:metabolism; D007364:Intercalating Agents / Q000138:chemical synthesis / Q000494:pharmacology; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D010963:Plasmodium falciparum / Q000187:drug effects / Q000201:enzymology; D011804:Quinolines / Q000494:pharmacology*; D013329:Structure-Activity Relationship
D000962:Antimalarials; D007364:Intercalating Agents; D011804:Quinolines; D002738:Chloroquine; D004247:DNA; D007770:L-Lactate Dehydrogenase; D004996:Ethidium