title: Structure-based design of nitrosoureas containing tyrosine derivatives as potential antimelanoma agents.
abstract: Two new nitrosoureas (TNUs), containing tyrosine derivatives as carriers of nitrosourea cytotoxic group have been synthesised. The physicochemical properties such as half-life time (tau(0.5)), alkylating and carbamoylating activities were determined. The nitrosoureas showed a higher inhibiting effect on the DOPA-oxidase activity of mushroom tyrosinase than that of the antitumour drug N'-cyclohexyl-N-(2-chloroethyl)-N-nitrosourea (lomustine, CCNU). In vitro cytotoxic effects of newly synthesised tyrosine containing nitrosoureas have been studied and compared to those of CCNU. A higher cytotoxicity to B16 melanoma cells than to YAC-1 and to lymphocytes was demonstrated for the tyrosine containing nitrosoureas in comparison with CCNU. Based on the results presented, we accept that a new trend for synthesis of more selective and less toxic nitrosourea derivatives as potential antimelanomic drugs might be developed.
authors.affiliation: Department of Chemistry and Biochemistry, Medical Faculty, Thracian University, 11 Armeiska Street, BG-6000 Stara Zagora, Bulgaria. vgadjeva@mf.uni-sz.bg
authors.forename: Vesselina
authors.initials: V
authors.lastname: Gadjeva
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D018906:Antineoplastic Agents, Alkylating / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D002219:Carbamates / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects; D004354:Drug Screening Assays, Antitumor; D006207:Half-Life; D006801:Humans; D066298:In Vitro Techniques; D008214:Lymphocytes / Q000166:cytology / Q000187:drug effects; D008546:Melanoma, Experimental; D014442:Monophenol Monooxygenase / Q000037:antagonists & inhibitors; D009607:Nitrosourea Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology
chemical_list: D000970:Antineoplastic Agents; D018906:Antineoplastic Agents, Alkylating; D002219:Carbamates; D009607:Nitrosourea Compounds; D014443:Tyrosine; D014442:Monophenol Monooxygenase; C070766:carbamic acid