Comparison of the cytotoxicity of two nitroheterociclic drugs (NHCD) towards transformed and non-transformed cells

The cytotoxicity of two nitroheterocyclic compounds (NHCD), Nitracrine, 1-nitro-9(3'3-dimethylaminopropylamino) acridine (Polfa, Poland) and Quinifuryl, 2-(5'-nitro-2-furanyl) ethenyl-4-{N-[4-(N,N-diethylamino)-1'-methylbutyl] carbamoyl}quinoline (Dr. N. M. Sukhova, Institute of Organic Synthesis, Riga, Latvian Republic), towards two lines of leukaemic cells and a line of non-transformed cells, was determined under normoxia conditions. Although both drugs showed significant cytotoxicity to all cell lines (LC50 for 24 h, less than or equal to2 muM) with that of Nitracrine exceeding Quinifuryl, their toxicity towards murine leukaemia P388 was substantially higher, compared to murine fibroblasts NIH3T3. In addition, the rate of cell death was also two- to three-fold higher in case of P388 cells versus NIH3T3. Interestingly, human erythroleukaemia K562 cells were shown to uptake the drugs 10 min after their addition to the tissue culture medium, while the LC50 values were reached after a substantial delay of 3 h. This delay might be due to the intracellular transformation of drugs required for cell killing. (C) 2003 Elsevier Ltd. All rights reserved.