Sample records for chlorouracils

  1. Discovery of 5-substituted-6-chlorouracils as novel thymidine phosphorylase inhibitors

    Czech Academy of Sciences Publication Activity Database

    Nencka, Radim; Votruba, Ivan; Hřebabecký, Hubert; Tloušťová, Eva; Masojídková, Milena; Holý, Antonín

    Bern : DCB University of Bern, 2006. s. 224. [IRT-International Roundtable on Nucleosides, Nucleotides and Nucleic Acids /17./. 03.09.2006-07.09.2006, Bern] R&D Projects: GA MŠk(CZ) 1M0508 Institutional research plan: CEZ:AV0Z40550506 Keywords : thymidine phosphorylase * 5-substituted-6-chlorouracils * angiogenesis Subject RIV: CC - Organic Chemistry

  2. Synthesis of [6-36Cl]chlorouracil, [6-82Br]bromouracil and [6-123I]iodouracil

    International Nuclear Information System (INIS)

    Three C-6 radiohalogenated uracil derivatives were prepared by non-isotopic halogen exchange reactions for evaluation as diagnostic radiopharmaceuticals. [6-36Cl]chlorouracil (radiochemical yield 77%, specific activity 5.66 MBq mmol-1) was prepared via calcium [36Cl]chloride exchange on 6-iodouracil, [6-82Br]bromouracil (27%, 68.4 MBq mmol-1) was prepared via ammonium [82Br]bromide exchange on 6-iodouracil and [6-123I]iodouracil (55.4%, 5.41 GBq mmol-1) was prepared via sodium [123I]iodide exchange on 6-chlorouracil. The specific activities and radiochemical yields were dependent upon the halide-ion concentration. (author)

  3. Discovery of 5-substituted-6-chlorouracils as efficient inhibitors of human thymidine phosphorylase

    Czech Academy of Sciences Publication Activity Database

    Nencka, Radim; Votruba, Ivan; Hřebabecký, Hubert; Jansa, Petr; Tloušťová, Eva; Horská, Květoslava; Masojídková, Milena; Holý, Antonín


    Roč. 50, č. 24 (2007), s. 6016-6023. ISSN 0022-2623 R&D Projects: GA MŠk 1M0508; GA AV ČR 1QS400550501 Institutional research plan: CEZ:AV0Z40550506 Keywords : thymidine phosphorylase inhibitors Subject RIV: CC - Organic Chemistry Impact factor: 4.895, year: 2007

  4. Structure, stability and function of 5-chlorouracil modified A:U and G:U base pairs

    Energy Technology Data Exchange (ETDEWEB)

    Patra, Amritraj [Vanderbilt Univ., Nashville, TN (United States); Harp, Joel [Vanderbilt Univ., Nashville, TN (United States); Pallan, Pradeep S. [Vanderbilt Univ., Nashville, TN (United States); Zhao, Linlin [Vanderbilt Univ., Nashville, TN (United States); Abramov, Mikhail [Rega Inst. for Medical Research (Belgium); Herdewijn, Piet [Rega Inst. for Medical Research (Belgium); Univ. of Evry-Val-d' Essonne (France); Egli, Martin [Vanderbilt Univ., Nashville, TN (United States)


    The thymine analog 5-chlorouridine, first reported in the 1950s as anti-tumor agent, is known as an effective mutagen, clastogen and toxicant as well as an effective inducer of sister-chromatid exchange. Recently, the first microorganism with a chemically different genome was reported; the selected Escherichia coli strain relies on the four building blocks 5-chloro-2'-deoxyuridine (ClU), A, C and G instead of the standard T, A, C, G alphabet [Marlière,P., Patrouix,J., Döring,V., Herdewijn,P., Tricot,S., Cruveiller,S., Bouzon,M. and Mutzel,R. (2011) Chemical evolution of a bacterium’s genome. Angew. Chem. Int. Ed., 50, 7109–7114]. The residual fraction of T in the DNA of adapted bacteria was <2% and the switch from T to ClU was accompanied by a massive number of mutations, including >1500 A to G or G to A transitions in a culture. The former is most likely due to wobble base pairing between ClU and G, which may be more common for ClU than T. To identify potential changes in the geometries of base pairs and duplexes as a result of replacement of T by ClU, we determined four crystal structures of a B-form DNA dodecamer duplex containing ClU:A or ClU:G base pairs. The structures reveal nearly identical geometries of these pairs compared with T:A or T:G, respectively, and no consequences for stability and cleavage by an endonuclease (EcoRI). The lack of significant changes in the geometry of ClU:A and ClU:G base pairs relative to the corresponding native pairs is consistent with the sustained unlimited self-reproduction of E. coli strains with virtually complete T→ClU genome substitution.

  5. Evaluation of the SOS chromotest for the detection of antimutagens

    International Nuclear Information System (INIS)

    The SOS chromotest was applied for the detection of antimutagens. To raise SOS induction, the bacteria were treated with the mutagens, UV, 4-nitroquinoline N-oxide (4NQO), N-methyl-N'-nitro-N-nitroso-guanidine (MNNG), or benzo[a]pyrene (B[a]p). The inhibitory effects of L-ascorbic acid, glutathione, vanillin,5-fluorouracil (5-FU), 5-chlorouracil (5-CU), cobaltous chloride, sodium selenite and sodium arsenite, which are known as antimutagens, were investigated with their addition either simultaneously or post treatment time. In became clear that the SOS chromotest was very useful for the detection of antimutagens

  6. Comparative study of HOCl-inflicted damage to bacterial DNA ex vivo and within cells. (United States)

    Suquet, Christine; Warren, Jeffrey J; Seth, Nimulrith; Hurst, James K


    The prospects for using bacterial DNA as an intrinsic probe for HOCl and secondary oxidants/chlorinating agents associated with it has been evaluated using both in vitro and in vivo studies. Single-strand and double-strand breaks occurred in bare plasmid DNA that had been exposed to high levels of HOCl, although these reactions were very inefficient compared to polynucleotide chain cleavage caused by the OH.-generating reagent, peroxynitrite. Plasmid nicking was not increased when intact Escherichia coli were exposed to HOCl; rather, the amount of recoverable plasmid diminished in a dose-dependent manner. At concentration levels of HOCl exceeding lethal doses, genomic bacterial DNA underwent extensive fragmentation and the amount of precipitable DNA-protein complexes increased several-fold. The 5-chlorocytosine content of plasmid and genomic DNA isolated from HOCl-exposed E. coli was also slightly elevated above controls, as measured by mass spectrometry of the deaminated product, 5-chlorouracil. However, the yields were not dose-dependent over the bactericidal concentration range. Genomic DNA recovered from E. coli that had been subjected to phagocytosis by human neutrophils occasionally showed small increases in 5-chlorocytosine content when compared to analogous cellular reactions where myeloperoxidase activity was inhibited by azide ion. Overall, the amount of isolable 5-chlorouracil from the HOCl-exposed bacterial cells was far less than the damage manifested in polynucleotide bond cleavage and cross-linking. PMID:19850004

  7. In search of uracil derivatives as bioactive agents. Uracils and fused uracils: Synthesis, biological activity and applications. (United States)

    Pałasz, Aleksandra; Cież, Dariusz


    This review article is an effort to summarize recent developments in researches providing uracil derivatives with promising biological potential. This article also aims to discuss potential future directions on the development of more potent and specific uracil analogues for various biological targets. Uracils are considered as privileged structures in drug discovery with a wide array of biological activities and synthetic accessibility. Antiviral and anti-tumour are the two most widely reported activities of uracil analogues however they also possess herbicidal, insecticidal and bactericidal activities. Their antiviral potential is based on the inhibition of key step in viral replication pathway resulting in potent activities against HIV, hepatitis B and C, the herpes viruses etc. Uracil derivatives such as 5-fluorouracil or 5-chlorouracil were the first pharmacological active derivatives to be generated. Poor selectivity limits its therapeutic application, resulting in high incidences of gastrointestinal tract or central nervous toxicity. Numerous modifications of uracil structure have been performed to tackle these problems resulting in the development of derivatives exhibiting better pharmacological and pharmacokinetic properties including increased bioactivity, selectivity, metabolic stability, absorption and lower toxicity. Researches of new uracils and fused uracil derivatives as bioactive agents are related with modifications of substituents at N(1), N(3), C(5) and C(6) positions of pyrimidine ring. This review is an endeavour to highlight the progress in the chemistry and biological activity of the uracils, predominately after the year 2000. In particular are presented synthetic methods and biological study for such analogues as: 5-fluorouracil or 5-chlorouracil derivatives, tegafur analogues, arabinopyranonucleosides of uracil, glucopyranonucleosides of uracil, liposidomycins, caprazamycins or tunicamycins, tritylated uridine analogues, nitro or cyano