title: Comparison of the cytotoxicity of two nitroheterocyclic drugs (NHCD) towards transformed and non-transformed cells.
abstract: 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 (LC(50) for 24h, < or = 2 microM) 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 LC(50) values were reached after a substantial delay of 3h. This delay might be due to the intracellular transformation of drugs required for cell killing.
authors.affiliation: Department of Physiological Sciences, Federal University of São Carlos, São Carlos, Brazil.
authors.forename: Marcelo M
authors.initials: MM
authors.lastname: Rossa
authors.forename: Thomaz A A
authors.initials: TA
authors.lastname: Rocha-e-Silva
authors.forename: Cristina H B
authors.initials: CH
authors.lastname: Terruggi
authors.forename: Antonio C
authors.initials: AC
authors.lastname: Tedesco
authors.forename: Heloisa S
authors.initials: HS
authors.lastname: Selistre-de-Araujo
authors.forename: Iouri E
authors.initials: IE
authors.lastname: Borissevich
authors.forename: Igor A
authors.initials: IA
authors.lastname: Degterev
mesh_terms: D000818:Animals; D015687:Cell Hypoxia / Q000187:drug effects; D002460:Cell Line; D002461:Cell Line, Transformed; D006801:Humans; D020014:K562 Cells / Q000187:drug effects; D007941:Leukemia P388 / Q000378:metabolism; D051379:Mice; D041681:NIH 3T3 Cells / Q000187:drug effects; D009564:Nitracrine / Q000009:adverse effects*; D011804:Quinolines / Q000009:adverse effects*; D014407:Tumor Cells, Cultured
chemical_list: D011804:Quinolines; C099760:quinifuryl; D009564:Nitracrine