Cytotoxicity of novel trifluoromethylquinoline derivatives on human leukemia cells.
This report is a comparative study of the in vitro cell-growth inhibitory activity of six new trifluoromethylquinoline derivatives on human promyelocytic leukemic cells and the evaluation of their DNA binding characteristics. 2,8-Bis(trifluoromethyl)quinoline-4-(N(4)-ethyl-5-nitroimidazolo)methylene ketone shows the highest cell-growth inhibitory activity with IC(50) of 10+/-2.5 microM, causes extensive changes in the morphology of the HL-60 cells and appears to induce apoptosis. The other compounds are only moderately growth-inhibitory, while 8-trifluoromethylquinoline-4-(N(4)-ethyl-5-nitroimidazolo)methylene ketone is actually stimulatory to cell growth. Except for the latter, the cell growth inhibitory activity of these compounds appears to be due their ability to bind to and intercalate DNA.
Department of Pharmaceutical Chemistry, University of the North, Private Bag X1106, Sovenga 0717, South Africa. kgokongj@unin.unorth.ac.za
J L
JL
Kgokong
J M
JM
Wachira
D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D004273:DNA, Neoplasm / Q000187:drug effects* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000378:metabolism; D004996:Ethidium / Q000378:metabolism; D018922:HL-60 Cells / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D011804:Quinolines / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
D004273:DNA, Neoplasm; D004791:Enzyme Inhibitors; D011804:Quinolines; D004996:Ethidium