Spin-labeled 1-alkyl-1-nitrosourea synergists of antitumor antibiotics.
A new method for synthesis of four spin-labeled structural analogues of the antitumor drug 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU), using ethyl nitrite for nitrosation of the intermediate spin-labeled ureas has been described. In vitro synergistic effects of 1-ethyl-3-[4-(2,2,6,6-tetramethylpiperidine-1-oxyl)]-1-nitrosourea (3b) on the cytotoxicity of bleomycin and farmorubicin were found in human lymphoid leukemia tumor cells. We measured the tissue distribution of 3b in organ homogenates of C57BL mice by an electron paramagnetic resonance method. The spin-labeled nitrosourea was mainly localized in the lungs. Our results strongly support the development and validation of a new approach for synthesis of less toxic nitrosourea derivatives as potential synergists of antitumor drugs.
Gadjeva
V
V
Department of Chemistry and Biochemistry, Medical Faculty, Stara Zagora, Bulgaria. vgadjeva@mf.uni-sz.bg
Koldamova
R
R
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology*; D018906:Antineoplastic Agents, Alkylating / Q000138:chemical synthesis / Q000493:pharmacokinetics / Q000494:pharmacology*; D001761:Bleomycin / Q000494:pharmacology; D002470:Cell Survival; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D004357:Drug Synergism; D015251:Epirubicin / Q000494:pharmacology; D016166:Free Radical Scavengers / Q000138:chemical synthesis / Q000494:pharmacology; D006207:Half-Life; D019337:Hematologic Neoplasms / Q000188:drug therapy; D006801:Humans; D007938:Leukemia / Q000188:drug therapy; D008130:Lomustine / Q000031:analogs & derivatives; D008214:Lymphocytes / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D009607:Nitrosourea Compounds / Q000138:chemical synthesis / Q000493:pharmacokinetics / Q000494:pharmacology*; D013113:Spin Labels; D014018:Tissue Distribution; D014407:Tumor Cells, Cultured
D000903:Antibiotics, Antineoplastic; D018906:Antineoplastic Agents, Alkylating; D016166:Free Radical Scavengers; D009607:Nitrosourea Compounds; D013113:Spin Labels; D001761:Bleomycin; D015251:Epirubicin; D008130:Lomustine