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Sample records for 5-fluoro pyrimidines labels

  1. 2-Chloro-5-fluoro-6-methyl-N-o-tolyl­pyrimidin-4-amine

    Jiang, Yufei; Wu, Kong; Cui, Dongmei; Zhou, Wei

    2013-01-01

    In the title compound, C12H11ClFN3, the benzene ring forms a dihedral angle of 72.43 (5)° with the pyrimidine ring. In the crystal, N—H⋯N hydrogen bonds link the mol­ecules into a chain running along the c axis.

  2. 2-Chloro-5-fluoro-6-methyl-N-o-tolyl­pyrimidin-4-amine

    Jiang, Yufei; Wu, Kong; Cui, Dongmei; Zhou, Wei

    2013-01-01

    In the title compound, C12H11ClFN3, the benzene ring forms a dihedral angle of 72.43 (5)° with the pyrimidine ring. In the crystal, N—H⋯N hydrogen bonds link the mol­ecules into a chain running along the c axis. PMID:23723793

  3. Isotope exchange reactions of the hydrogen H-5 of selected pyrimidine derivatives and the preparation of tritium-labeled pyrimidines

    Dračínský, Martin; Jansa, Petr; Elbert, Tomáš

    2011-01-01

    Roč. 76, č. 12 (2011), s. 1567-1577. ISSN 0010-0765 R&D Projects: GA AV ČR KJB400550903; GA MŠk 1M0508 Institutional research plan: CEZ:AV0Z40550506 Keywords : isotopic labeling * NMR spectroscopy * nucleobases * pyrimidines Subject RIV: CC - Organic Chemistry Impact factor: 1.283, year: 2011

  4. Synthesis of H-3 labeled 5-fluoro-3-[3-[4-(5-methoxy-4-pyrimidinyl)-1-piperazinyl]propyl]-1 H-indole, a serotonergic agent with potential antidepressant activity

    Dischino, D.D.; Combrink, K.D.; Doweyko, Lidia; Pearce, B.C.; Yevich, J.P. [Bristol-Myers Squibb Pharmaceutical Research Inst., Wallingford, CT (United States); Morimoto, Hiromi; Williams, P.G. [Lawrence Berkeley Lab., CA (United States)

    1995-12-31

    The title compound was prepared by the LiAlT{sub 4} reduction of 5-fluoro-3-[3-[4-(5-methoxy-4-pyrimidinyl)-1-piperazinyl]-3-oxoprop yl]-1H-indole. The radiochemical purity of the product was 98.9% and the specific activity was calculated as 53.0 Ci/mmol from HPLC analyses and 55.6 Ci/mmol from {sup 3}H NMR measurements. (Author).

  5. Kinetics of cell labeling and thymidine replacement after continuous infusion of halogenated pyrimidines in vivo

    Rodriguez, R.; Ritter, M.A.; Fowler, J.F.; Kinsella, T.J. (Univ. of Wisconsin Medical School, Madison, WI (United States))

    1994-04-30

    The authors present experiments on an in vivo human tumor xenograft continuously exposed to a fixed serum concentration of halogenated pyrimidines so as to study the kinetics of cell labeling and thymidine replacement. Human colon tumor (HCT-116) cells were injected subcutaneously into nude mice. After 10 days, most animals (>90%) developed measurable tumor nodules with a volume doubling time of 5 [+-] 1 days. Once the tumors reached a cross-sectional area of 0.25-0.30 cm[sup 2], miniosmotic pumps were implanted to deliver a dose of 100 mg/kg/day of IdUrd (iododeoxyuridine) by continuous infusion. After an IdUrd exposure time of 1-7 days, blood and tumor tissue were collected. The steady state serum IdUrd concentration was 0.95 [+-] 0.1 [mu]M, which is a clinically relevant concentration for a prolonged continuous intravenous infusion. The tumor cell potential doubling time (T[sub pot]) was 25. The percent IdUrd thymidine replacement and the fraction of cells labeled followed exponential saturation kinetics with a halflife of 33 and 27 h, respectively. After 5 days of exposure, the thymidine replacement in tumor cells was 2.0% and the fraction of tumor cells labeled was 94%. Immunohistochemical staining of IdUrd labeled tumor tissues showed an exposure-dependent gradient of cellular labeling that was initially highest in regions close to blood vessels. After 4 days of exposure at 100 mg/kg/day, there was an increase in the fraction of cells in G[sub 0] + G[sub 1] and a decrease in the S phase population, suggesting a block between G[sub 1] and S phase. They conclude that the in vivo kinetics of IdUrd thymidine replacement and fraction of cells labeled after continuous exposure followed exponential saturation kinetics with a halflife of approximately the potential doubling time of the tumor cell population. Some form of prolonged, or briefly interrupted, continuous infusion should be considered for clinical administration. 48 refs., 5 figs.

  6. Crystal structure of 4-amino-5-fluoro-2-oxo-2,3-dihydropyrimidin-1-ium 3-hydroxypyridine-2-carboxylate

    Ammasai Karthikeyan

    2014-11-01

    Full Text Available The asymmetric unit of the title salt, C4H5FN3O+·C6H4NO3−, contains one 4-amino-5-fluoro-2-oxo-2,3-dihydropyrimidin-1-ium (5-fluorocytosinium, 5FC cation and a 3-hydroxypicolinate (3HAP anion. The 4-amino-5-fluoro-2-oxo-2,3-dihydropyrimidine molecule is protonated at one of the pyrimidine N atoms. The typical intramolecular N—H...F and O—H...O S(5 and S(6 hydrogen-bond ring motifs are observed in the cations and anions. The protonated N atom and 2-amine group of the 5FC cation interact with the 3HPA anion through a pair of nearly parallel N—H...O hydrogen bonds, forming a robust R22(8 ring motif. The ions are further linked by N—H...N, O—H...O, N—H...O and C—H...O hydrogen bonds, generating R22(7, R33(12 and R65(18 ring motifs, respectively, leading to supramolecular wave-like sheets parallel to (010. The crystal structure is further stabilized by C—H...π interactions, generating a three-dimensional architecture.

  7. 2-(5-Fluoro-3-isopropylsulfanyl-7-methyl-1-benzofuran-2-ylacetic acid

    Hong Dae Choi

    2012-04-01

    Full Text Available The title compound, C14H15FO3S, was prepared by alkaline hydrolysis of ethyl 2-(5-fluoro-3-isopropylsulfanyl-7-methyl-1-benzofuran-2-ylacetate. In the crystal, molecules are linked via pairs of O—H...O hydrogen bonds, forming inversion dimers. These dimers are connected by weak C—H...O hydrogen bonds.

  8. Synthesis, characterization and antibacterial studies of 2-chloro-5-fluoro-N-[dibenzyl carbamothioyl] benzamide thiourea

    Sapari, Suhaila; Yamin, Bohari M.; Hasbullah, Aishah; Ibrahim, Nazlina [School of Chemical Science and Food Technology, Faculty of Science and Technology, The National University of Malaysia, 43600, Bangi, Selangor (Malaysia)

    2014-09-03

    Synthesis, characterization and antibacterial studies of 2-chloro-5-fluoro-N-[dibenzyl carbamothioyl] benzamide thiourea has been reported. The compound characterized by using elementary analysis CHNS, IR, {sup 1}H NMR and {sup 13}C NMR spectroscopies. The compounds have been screened for their antibacterial studies.

  9. Extracellular palladium-catalysed dealkylation of 5-fluoro-1-propargyl-uracil as a bioorthogonally activated prodrug approach

    Weiss, Jason T.; Dawson, John C.; MacLeod, Kenneth G.; Rybski, Witold; Fraser, Craig; Torres-Sánchez, Carmen; Patton, E. Elizabeth; Bradley, Mark; Carragher, Neil O.; Unciti-Broceta, Asier

    2014-02-01

    A bioorthogonal organometallic reaction is a biocompatible transformation undergone by a synthetic material exclusively through the mediation of a non-biotic metal source; a selective process used to label biomolecules and activate probes in biological environs. Here we report the in vitro bioorthogonal generation of 5-fluorouracil from a biologically inert precursor by heterogeneous Pd0 catalysis. Although independently harmless, combined treatment of 5-fluoro-1-propargyl-uracil and Pd0-functionalized resins exhibits comparable antiproliferative properties to the unmodified drug in colorectal and pancreatic cancer cells. Live-cell imaging and immunoassay studies demonstrate that the cytotoxic activity of the prodrug/Pd0-resin combination is due to the in situ generation of 5-fluorouracil. Pd0-resins can be carefully implanted in the yolk sac of zebrafish embryos and display excellent biocompatibility and local catalytic activity. The in vitro efficacy shown by this masking/activation strategy underlines its potential to develop a bioorthogonally activated prodrug approach and supports further in vivo investigations.

  10. Enthalpy of formation of 5-fluoro-1,3-dimethyluracil: 5-Fluorouracil revisited

    Highlights: • Enthalpies of formation measured by rotating bomb combustion calorimetry. • Sublimation enthalpies determined by the Knudsen mass-loss effusion technique. • Quantum chemical calculations allowed estimation of ΔfHmo (g). • New values of enthalpies of formation for 5-fluorouracil are recommended. - Abstract: In the present work, a re-determination of thermochemical data for 5-fluorouracil was performed and a new determination of thermochemical parameters for 5-fluoro-1,3-dimethyluracil are presented. The standard (po = 0.1 MPa) molar enthalpies of formation, in the crystalline phase, of 5-fluorouracil and 5-fluoro-1,3-dimethyluracil, at T = 298.15 K, were derived from the standard molar energies of combustion in oxygen, measured by rotating bomb combustion calorimetry. For these compounds, the standard molar enthalpies of sublimation, at T = 298.15 K, were determined from the temperature-vapour pressure dependence, obtained by the Knudsen mass-loss effusion method. Using the values for the heat capacity differences between the gas and the crystalline phases of the compounds studied, the standard (po = 0.1 MPa) molar enthalpies, entropies and Gibbs free energies of sublimation, at T = 298.15 K, were derived. From the experimentally determined values, the standard molar enthalpies of formation, in the gas phase, at T = 298.15 K, of 5-fluorouracil and 5-fluoro-1,3-dimethyluracil were calculated as −(454.5 ± 1.6) and −(478.5 ± 1.3) kJ · mol−1, respectively. These values were compared with estimates obtained from very accurate theoretical calculations using the G3(MP2)//B3LYP composite method and appropriately chosen reactions

  11. Cellular pharmacology of multi- and duplex drugs consisting of ethynylcytidine and 5-fluoro-2'-deoxyuridine

    Bijnsdorp, I.V.; Schwendener, R. A.; Schott, H; Fichtner, I.; Smid, K; Laan, A.C.; Schott, S.; Losekoot, N; Honeywell, R.J.; Peters, G. J.

    2011-01-01

    Prodrugs can have the advantage over parent drugs in increased activation and cellular uptake. The multidrug ETC-L-FdUrd and the duplex drug ETC-FdUrd are composed of two different monophosphate-nucleosides, 5-fluoro-2'deoxyuridine (FdUrd) and ethynylcytidine (ETC), coupled via a glycerolipid or phosphodiester, respectively. The aim of the study was to determine cytotoxicity levels and mode of drug cleavage. Moreover, we determined whether a liposomal formulation of ETC-L-FdUrd would improve ...

  12. Cellular pharmacology of multi- and duplex drugsconsisting of ethynylcytidine and 5-fluoro-2'-deoxyuridine

    Bijnsdorp, I.V.; Schwendener, R. A.; Schott, H; Fichtner, I.; Smid, K; Laan, A.C.; Schott, S.; Losekoot, N; Honeywell, R.J.; Peters, G. J.

    2011-01-01

    Prodrugs can have the advantage over parent drugs in increased activation and cellular uptake. The multidrug ETC-L-FdUrd and the duplex drug ETC-FdUrd are composed of two different monophosphate-nucleosides, 5-fluoro-2'deoxyuridine (FdUrd) and ethynylcytidine (ETC), coupled via a glycerolipid or phosphodiester, respectively. The aim of the study was to determine cytotoxicity levels and mode of drug cleavage. Moreover, we determined whether a liposomal formulation of ETC-L-FdUrd would improve ...

  13. Synthesis and anticancer activity of some 5-fluoro-2'-deoxyuridine phosphoramidates.

    Lewandowska, Marta; Ruszkowski, Piotr; Chojnacka, Kinga; Kleczewska, Natalia; Hoffmann, Marcin; Kacprzak, Karol; Celewicz, Lech

    2016-05-15

    Two series of novel 4-chlorophenyl N-alkyl phosphoramidates of 3'-O-(t-butoxycarbonyl)-5-fluoro-2'-deoxyuridine (3'-BOC-FdU) (9a-9j) and 5-fluoro-2'-deoxyuridine (FdU) (10a-10j) were synthesized by means of phosphorylation of 3'-BOC-FdU (4) with 4-chlorophenyl phosphoroditriazolide (7), followed by a reaction with the appropriate amine. Phosphoramidates 9a-9j were converted to the corresponding 10a-10j by removal of the 3'-t-butoxycarbonyl protecting group (BOC) under acidic conditions. The synthesized phosphoramidates 9a-9j and 10a-10j were evaluated for their cytotoxic activity in five human cancer cell lines: cervical (HeLa), nasopharyngeal (KB), breast (MCF-7), liver (HepG2), osteosarcoma (143B) and normal human dermal fibroblast cell line (HDF) using the sulforhodamine B (SRB) assay. Two phosphoramidates 9b and 9j with the N-ethyl and N-(methoxy-(S)-alaninyl) substituents, respectively, displayed remarkable activity in all the investigated cancer cells, and the activity was considerably higher than that of the parent nucleoside 4 and FdU. Among phosphoramidates 10a-10j compound 10c with the N-(2,2,2-trifluoroethyl) substituent showed the highest activity. Phosphoramidate 10c was more active than the FdU in all the cancer cell lines tested. PMID:27073055

  14. Synthesis, Characterization, and Agricultural Biological Activities of 5-Fluoro-2-hydroxy Butyrophenone

    Fengli Xin

    2013-01-01

    Full Text Available A novel synthetic approach towards 5-fluoro-2-hydroxy butyrophenone is reported. Using 4-fluorophenol as a raw material, the processes of etherification protection, Friedel-Crafts acylation and demethylation provide the target compound under mild conditions. The structure was characterized by the melting point and IR, MS, 1H-NMR, and 13C-NMR spectroscopy. The bioassay results indicate that the target compound exhibits potent antifungal activities against Valsa mali, Coniella dipodiella, and other agricultural plant fungi. The target compound also shows potent herbicidal activities for Lactuca sativa, a dicotyledon, and Echinochloa crus-galli, a monocotyledon. The toxicity regression C50 values of the compound against Valsa mali, Coniothyrium diplodiella, Lactuca sativa seedling, and Echinochloa crusgalli seedling were calculated by SPSS. The Hormesis effect for roots of Echinochloa crusgalli was confirmed.

  15. Synthesis of hypoxia imaging agent 1-(5-deoxy-5-fluoro-{alpha}-D-arabinofuranosyl)-2-nitroimidazole using microfluidic technology

    Bouvet, Vincent R.; Wuest, Melinda; Wiebe, Leonard I.; Wuest, Frank, E-mail: wuest@ualberta.c

    2011-02-15

    Introduction: Microfluidic technology allows fast reactions in a simple experimental setup, while using very low volumes and amounts of starting material. Consequently, microfluidic technology is an ideal tool for radiolabeling reactions involving short-lived positron emitters. Optimization of the complex array of different reaction conditions requires knowledge of the different reaction parameters linked to the microfluidic system as well as their influence on the radiochemical yields. 1-(5-Deoxy-5-fluoro-{alpha}-D-arabinofuranosyl)-2-nitroimidazole ([{sup 18}F]FAZA) is a frequently used radiotracer for PET imaging of tumor hypoxia. The present study describes the radiosynthesis of [{sup 18}F]FAZA by means of microfluidic technology and subsequent small animal PET imaging in EMT-6 tumor-bearing mice. Methods: Radiosyntheses were performed using the NanoTek Microfluidic Synthesis System (Advion BioSciences, Inc.). Optimal reaction conditions were studied through screening different reaction parameters like temperature, flow rate, residency time, concentration of the labeling precursor (1-(2,3-di-O-acetyl-5-O-tosyl-{alpha}-D-arabinofuranosyl)-2-nitroimidazole) and the applied volume ratio between the labeling precursor and [{sup 18}F]fluoride. Results: Optimized reaction conditions at low radioactivity levels (1 to 50 MBq) afforded 63% (decay-corrected) of HPLC-purified [{sup 18}F]FAZA within 25 min. Higher radioactivity levels (0.4 to 2.1 GBq) gave HPLC-purified [{sup 18}F]FAZA in radiochemical yields of 40% (decay-corrected) within 60 min at a specific activity in the range of 70 to 150 GBq/{mu}mol. Small animal PET studies in EMT-6 tumor-bearing mice showed radioactivity accumulation in the tumor (SUV{sub 20min} 0.74 {+-} 0.08) resulting in an increasing tumor-to-muscle ratio over time. Conclusions: Microfluidic technology is an ideal method for the rapid and efficient radiosynthesis of [{sup 18}F]FAZA for preclinical radiopharmacological studies. Careful

  16. Synthesis of hypoxia imaging agent 1-(5-deoxy-5-fluoro-α-D-arabinofuranosyl)-2-nitroimidazole using microfluidic technology

    Introduction: Microfluidic technology allows fast reactions in a simple experimental setup, while using very low volumes and amounts of starting material. Consequently, microfluidic technology is an ideal tool for radiolabeling reactions involving short-lived positron emitters. Optimization of the complex array of different reaction conditions requires knowledge of the different reaction parameters linked to the microfluidic system as well as their influence on the radiochemical yields. 1-(5-Deoxy-5-fluoro-α-D-arabinofuranosyl)-2-nitroimidazole ([18F]FAZA) is a frequently used radiotracer for PET imaging of tumor hypoxia. The present study describes the radiosynthesis of [18F]FAZA by means of microfluidic technology and subsequent small animal PET imaging in EMT-6 tumor-bearing mice. Methods: Radiosyntheses were performed using the NanoTek Microfluidic Synthesis System (Advion BioSciences, Inc.). Optimal reaction conditions were studied through screening different reaction parameters like temperature, flow rate, residency time, concentration of the labeling precursor (1-(2,3-di-O-acetyl-5-O-tosyl-α-D-arabinofuranosyl)-2-nitroimidazole) and the applied volume ratio between the labeling precursor and [18F]fluoride. Results: Optimized reaction conditions at low radioactivity levels (1 to 50 MBq) afforded 63% (decay-corrected) of HPLC-purified [18F]FAZA within 25 min. Higher radioactivity levels (0.4 to 2.1 GBq) gave HPLC-purified [18F]FAZA in radiochemical yields of 40% (decay-corrected) within 60 min at a specific activity in the range of 70 to 150 GBq/μmol. Small animal PET studies in EMT-6 tumor-bearing mice showed radioactivity accumulation in the tumor (SUV20min 0.74 ± 0.08) resulting in an increasing tumor-to-muscle ratio over time. Conclusions: Microfluidic technology is an ideal method for the rapid and efficient radiosynthesis of [18F]FAZA for preclinical radiopharmacological studies. Careful analysis of various reaction parameters is an important

  17. Investigations of the chemical consequences of radioactive decay of iodine 125 and tritium in labelled pyrimidine bases using the double labelling technique and ESR spectroscopy

    In the present work, the chemical secondary reactions of the radioactive decay (K capture) of I 125 in solutions of the synthetic DNA forerunner iodouracil were investigated with the aim to interpret the large radiotoxicity of DNA-bonded I 125 by procedures at molecular level. Furthermore, the radical formation as a result of the decay of tritium in 3H-labelled thymine and cytosine were also traced on a smaller scale. The chemical decay effects of molecular bonded iodine 125 was investigated using the double labelling technique (I 125 + C 14). After accumulation of the I 125 decays and hence the product molecules in aqueous solution at +20 or -1960C, the reaction products were radio-gas chromatographically separated or by means of high-pressure liquid chromatography and then analyzed. Radiolytic side effects were simultaneously determined by separate γ-irradiation experiments. The results show that due to the Auger effect as a result of the radioactive decay of 125I, a significantly greater destruction occurs in the immediate environment than can be achieved by external irradiation with γ-quanta. It could be shown for the first time, by detection of the volatile transmutation products CO and CO2, that drastic chemical consequences result for the molecule residue in the decay of molecular-bonded 125I even in the condensed phase. The β-autoradiolysis was also determined to be the main source of fragmentation in the case of tritium beta decay in thymine and cytosine. ESR investigations show distinct differences in the radical formation compared to external γ-radiolysis. (orig./RB)

  18. Synthesis and Anti-Hyperlipidemic Evaluation of N‑(Benzoylphenyl-5-fluoro-1H-indole-2-carboxamide Derivatives in Triton WR-1339-Induced Hyperlipidemic Rats

    Tariq Al-Qirim

    2010-08-01

    Full Text Available The lipid-lowering activity of a series of novel N-(benzoylphenyl-5-fluoro-1H-indole-2-carboxamide derivatives has been studied in Triton WR-1339-induced hyperlipidemia in rats. The test animals were divided into four groups: control, hyperlipidemic, compound + 4% DMSO [C1: N-(2-benzoylphenyl-5-fluoro-1H-indole-2-carboxamide (1, C2: N-(3-benzoylphenyl-5-fluoro-1H-indole-2-carboxamide (2, C3: N-(4-benzoylphenyl-5-fluoro-1H-indole-2-carboxamide (3]-treated and bezafibrate (BF-treated. At a dose of 15 mg/Kg body weight, compounds 2, 3 and BF significantly reduced elevated plasma triglycerodes levels after 12 h. Moreover, high density lipoprotein-cholesterol levels were significantly increased in all treated groups after 12 h compared to the hyperlipidemic control group, except for C1 which was inactive. In sum, it may be stated that the results of the present study demonstrated new properties of some N-(benzoylphenyl-5-fluoro-1H-indole-2-carboxamide derivatives as potent lipid lowering agents and these beneficial activities may contribute to their cardioprotective and antiatherosclerotic role.

  19. MicroRNA-351 Regulates Two-Types of Cell Death, Necrosis and Apoptosis, Induced by 5-fluoro-2'-deoxyuridine

    Omi, Takuya; Yamamoto, Akihiro; Satake, Akito; Hiramoto, Akiko; Masutani, Mitsuko; Tanuma, Sei-ichi; Wataya, Yusuke; Kim, Hye-Sook

    2016-01-01

    Cell-death can be necrosis and apoptosis. We are investigating the mechanisms regulating the cell death that occurs on treatment of mouse cancer cell-line FM3A with antitumor 5-fluoro-2'-deoxyuridine (FUdR): necrosis occurs for the original clone F28-7, and apoptosis for its variant F28-7-A. Here we report that a microRNA (miR-351) regulates the cell death pattern. The miR-351 is expressed strongly in F28-7-A but only weakly in F28-7. Induction of a higher expression of miR-351 in F28-7 by transfecting an miRNA mimic into F28-7 resulted in a change of the death mode; necrosis to apoptosis. Furthermore, transfection of an miR-351 inhibitor into F28-7-A resulted in the morphology change, apoptosis to necrosis, in this death-by-FUdR. Possible mechanism involving lamin B1 in this miR-351’s regulatory action is discussed. PMID:27071035

  20. Crystal structures of (E-N′-(2-hydroxy-5-methylbenzylideneisonicotinohydrazide and (E-N′-(5-fluoro-2-hydroxybenzylideneisonicotinohydrazide

    Kittipong Chainok

    2016-07-01

    Full Text Available Two derivatives of the well-known iron chelator, (E-N′-(2-hydroxybenzylideneisonicotinohydrazide (SIH, substituted in the 5-position of the 2-hydroxybenzene ring by a methyl and a fluorine group viz. (E-N′-(2-hydroxy-5-methylbenzylideneisonicotinohydrazide, C14H13N3O2, (I, and (E-N′-(5-fluoro-2-hydroxybenzylideneisonicotinohydrazide, C13H10FN3O2, (II, have been prepared and characterized by single-crystal X-ray diffraction, 1H NMR and mass spectrometry. The molecules of both compounds deviate slightly from planarity [r.m.s. deviations are 0.145 and 0.110 Å for (I and (II, respectively] and adopt an E conformation with respect to the double bond of the hydrazone bridge. In each molecule, there is an intramolecular O—H...N hydrogen bond forming an S(6 ring motif. The dihedral angles between the mean planes of the isonicotinoyl ring and the cresol ring in (I or the fluorophenol ring in (II are 10.49 (6 and 9.43 (6°, respectively. In the crystals of both compounds, zigzag chains are formed via N—H...N hydrogen bonds, in the [10-1] direction for (I and [010] for (II. In (I, the chains are linked by weak C—H...π and π–π stacking interactions [centroid-to-centroid distances = 3.6783 (8 Å; inter-planar angle = 10.94 (5°], leading to the formation of a three-dimensional supramolecular architecture. In (II, adjacent chains are connected through C—H...O hydrogen bonds to form sheets parallel to (100, which enclose R44(30 ring motifs. The sheets are linked by weak C—H...π and π–π [centroid-to-centroid distance = 3.7147 (8 Å; inter-planar angle = 10.94 (5°] interactions, forming a three-dimensional supramolecular architecture.

  1. Improved detection and measurement of low levels of [18F]fluoride metabolized from [18F]-labeled pyrimidine nucleoside analogues in biological samples

    Introduction: It is important to identify all circulating metabolites, including free fluoride, for accurate pharmacokinetic modeling of [18F]-labeled radiotracers. We sought to determine the most efficient method to detect and quantify low levels of free [18F]fluoride in biological samples. Methods: Low levels of [18F]fluoride were analyzed using two methods: (A) an ion-exchange cartridge and gamma counting, and (B) radio-HPLC, to compare the detection limits of these two analytical methods. Twenty microliters of [18F]fluoride solution was loaded onto an ion-exchange cartridge, then eluted with 20% MeCN/water (5 ml) and radioactivity trapped in the cartridge counted on a gamma counter. [18F]Fluoride was also determined in plasma and urine from mice injected with [18F]-labeled thymidine analogues using Method A. Results: The detection sensitivity of Method A was 9.4-fold higher than that of Method B (0.075±0.004 vs. 0.71±0.02 nCi). With Method A, [18F]fluoride was determined in plasma for [18F]FLT, [18F]FMAU, [18F]FEAU and N3-[18F]FPrT as 1.4±0.31% (n=4), 0.17±0.49% (n=3), 4.88±1.62% (n=3) and 12.94±0.48% (n=4), respectively. The amount of [18F]fluoride determined in the urine was 11.49±1.60% (n=4) from [18F]FLT, 5.36±2.34% (n=3) from [18F]FMAU, 13.57±1.96% (n=3) from [18F]FEAU and 11.19±1.98% (n=4) from N3-[18F]FPrT. Conclusion: Low levels of [18F]fluoride in biological samples can be detected and quantified using an ion-exchange cartridge and gamma counting. This methodology is simple, accurate and superior to the standard use of radio-HPLC on a C18 column for metabolite analysis, and it should be useful in pharmacokinetic modeling for animal imaging studies using an [18F]-labeled radiotracer and PET.

  2. Increased sensitivity to the prodrug 5'-deoxy-5-fluorouridine and modulation of 5-fluoro-2'-deoxyuridine sensitivity in MCF-7 cells transfected with thymidine phosphorylase.

    Patterson, A V; Zhang, H.; Moghaddam, A; Bicknell, R.; Talbot, D. C.; Stratford, I. J.; Harris, A. L.

    1995-01-01

    Platelet-derived endothelial cell growth factor (PD-ECGF) is identical to human thymidine phosphorylase (dThdPase). The human MCF-7 breast cancer cell line was transfected with the dThdPase cDNA and expressed a 45 kDa protein that was detected with anti-dThdPase antibody. Cell lysates possessed elevated dThdPase activity and cells had up to 165-fold increased sensitivity to the prodrug 5'-deoxy-5-fluorouridine (5'-DFUR) in vitro. Sensitivity to 5-fluorouracil (5-FU) and 5-fluoro-2'-deoxyuridi...

  3. Thiamin Pyrimidine Biosynthesis in Candida albicans: A Remarkable Reaction between Histidine and Pyridoxal Phosphate

    Lai, Rung-Yi; Huang, Siyu; Fenwick, Michael K.; Hazra, Amrita; Zhang, Yang; Rajashankar, Kanagalaghatta; Philmus, Benjamin; Kinsland, Cynthia; Sanders, Jennie Mansell; Ealick, Steven E.; Begley, Tadhg P. (Cornell); (TAM)

    2012-06-26

    In Saccharomyces cerevisiae, thiamin pyrimidine is formed from histidine and pyridoxal phosphate (PLP). The origin of all of the pyrimidine atoms has been previously determined using labeling studies and suggests that the pyrimidine is formed using remarkable chemistry that is without chemical or biochemical precedent. Here we report the overexpression of the closely related Candida albicans pyrimidine synthase (THI5p) and the reconstitution and preliminary characterization of the enzymatic activity. A structure of the C. albicans THI5p shows PLP bound at the active site via an imine with Lys62 and His66 in close proximity to the PLP. Our data suggest that His66 of the THI5 protein is the histidine source for pyrimidine formation and that the pyrimidine synthase is a single-turnover enzyme.

  4. 5-Fluoro-[β-11C]-L-tryptophan is a functional analogue of 5-hydroxy-[β-11C]-L-tryptophan in vitro but not in vivo

    Introduction: 5-Hydroxy-[β-11C]-L-tryptophan ([11C]HTP) is an established positron emission tomography (PET) imaging agent for neuroendocrine tumors (NETs). It has also been used for other clinical research purposes in neurology and diabetes. However, its widespread use is limited by the short physical half-life of the radionuclide and a difficult radiosynthesis. Therefore, a Fluorine-18 labeled analogue, 5-[18F]Fluoro-L-tryptophan ([18F]FTRP), has been proposed as a functional analogue. There is no published method for the synthesis of L-[18F]FTRP. We have therefore developed a synthesis of 5-fluoro-[β-11C]-L-tryptophan ([11C]FTRP), based on the existing chemo-enzymatic method for [11C]HTP and evaluated the potential usefulness of radiolabeled FTRP as a substitute for [11C]HTP. Methods: The in vitro and in vivo behavior of [11C]FTRP, including the dependence of key enzymes in the serotonergic metabolic pathway, was investigated in NET cell lines, NET xenograft carrying immunodeficient mice, normal rats and in non-human primate. [11C]HTP was used for direct comparison. Results: Uptake of [11C]FTRP in NET cell lines in vitro was mediated by enzymes involved in serotonin synthesis and metabolism, similar to [11C]HTP. In vivo biodistribution, either in rodent or non-human primate, was not affected by selectively inhibiting enzymatic steps in the serotonergic metabolic pathway. Conclusion: [11C]FTRP has in vitro biological function similar to that of [11C]HTP. However, this function is not retained in vivo as shown by biodistribution and PET/CT studies. Radiolabeled FTRP is thus not likely to provide an advantage over [11C]HTP in PET imaging in oncology, neurology or diabetes

  5. Synthesis, Characterization, Spectroscopic Properties of 2-(4-Dimethylaminophenyl)-5-fluoro-6-(morpholin-4-yl)-1H-benzimidazole and its Interaction with Calf Thymus DNA

    Ling Tian TANG; Yi WANG; Xin Qi LIU; Shao Wen HU; Tai Wei CHU; Xiang Yun WANG

    2005-01-01

    2-(4-Dimethylaminophenyl)-5-fluoro-6-(morpholin-4-yl)- 1H-benzimidazole(1) has been synthesized and characterized by 1H-NMR, MS and elemental analysis. UV-Vis spectra of the aqueous solutions at different pH values reveal that compound 1 can combine three protons. Its three protonation constants are determined by spectrophotometry and calculated by non-linear least squares. The results of steady-state fluorescence measurements indicate that a special interaction occurs between compound 1 and calf thymus DNA, of which the binding constant, Kb, is (2.30 ±0.10)×l04 L/mol. Compound 1 in the concentration range of 10-8 to 1.2×l0-6 mol/L could be used for quantitative determination of DNA.

  6. First chemotherapy by docetaxel, cisplatin and 5-fluoro-uracil (T.P.F.) followed by concomitant chemoradiotherapy in the treatment of cavum locally evolved undifferentiated carcinomas without metastases; Chimiotherapie premiere par docetaxel, cisplatine et 5-fluoro-uracile (TPF) suivie de chimioradiotherapie concomitante dans le traitement des carcinomes indifferencies localement evolues non metastatiques du cavum

    Sahli, B.; Bali, M.S.; Miles, I.; Djemaa, A. [CHU Benbadis, Constantine (Algeria)

    2009-10-15

    It is a prospective study in order to evaluate the feasibility and the toxicity of a chemotherapy by docetaxel, cisplatin and 5-fluoro-uracil followed by a concomitant chemoradiotherapy in the treatment of non metastatic locally evolved undifferentiated carcinomas of the cavum. The conclusion was despite the low number of patients in our series, the observed results show that this neoadjuvant chemotherapy followed by a concomitant chemoradiotherapy in the locally evolved undifferentiated carcinomas of the cavum is feasible. however, the high acute toxicity needs the use of conformal irradiation techniques. Besides, a longer follow up is necessary to evaluate the therapy efficiency and the delayed toxicity of this protocol. (N.C.)

  7. A Search for Interstellar Pyrimidine

    Kuan, Y J; Charnley, S B; Kisiel, Z; Ehrenfreund, P; Huang, H C; Kuan, Yi-Jehng; Yan, Chi-Hung; Charnley, Steven B.; Kisiel, Zbigniew; Ehrenfreund, Pascale; Huang, Hui-Chun

    2003-01-01

    We have searched three hot molecular cores for submillimeter emission from the nucleic acid building-block pyrimidine. We obtain upper limits to the total pyrimidine (beam-averaged) column densities towards Sgr B2(N), Orion KL and W51 e1/e2 of 1.7E+14 cm^{-2}, 2.4E+14 cm^{-2} and 3.4E+14 cm^{-2}, respectively. The associated upper limits to the pyrimidine fractional abundances lie in the range (0.3-3)E-10. Implications of this result for interstellar organic chemistry, and for the prospects of detecting nitrogen heterocycles in general, are briefly discussed.

  8. 5-Fluoro-1-[(4S,5R)-5-(2-hydroxyethyl)-2,2-dimethyl-1,3-dioxolan-4-yl]pyrimidine-2,4(1H,3H)-dione

    Angel Mendoza; Martha Sosa-Rivadeneyra; Fernando Sartillo-Piscil; Leticia Quintero; Marcos Flores-Alamo

    2010-01-01

    In the title compound, C11H15FN2O5, the five-membered ring has an envelope conformation, while the six-membered ring is essentially planar, with a maximum deviation of 0.032 (2) Å from the mean plane. The crystal packing is stabilized by intermolecular N—H...O and O—H...O hydrogen bonds, generating a layer structure parallel to (001).

  9. 5-Fluoro-1-[(4S,5R-5-(2-hydroxyethyl-2,2-dimethyl-1,3-dioxolan-4-yl]pyrimidine-2,4(1H,3H-dione

    Angel Mendoza

    2010-06-01

    Full Text Available In the title compound, C11H15FN2O5, the five-membered ring has an envelope conformation, while the six-membered ring is essentially planar, with a maximum deviation of 0.032 (2 Å from the mean plane. The crystal packing is stabilized by intermolecular N—H...O and O—H...O hydrogen bonds, generating a layer structure parallel to (001.

  10. Removal of uv-induced pyrimidine dimers from the replicated and unreplicated DNA of human fibroblasts

    Excision repair in uv irradiated human fibroblasts has been examined in portions of DNA replicating after irradiation versus those remaining unreplicated. Two approaches, one using a uv-endonuclease to estimate pyrimidine dimers remaining in DNA, the other using density labeling to measure excision resynthesis, indicate that the extent of repair is the same for both replicated and unreplicated DNA

  11. Polyurethane Foams with Pyrimidine Rings

    Kania Ewelina

    2014-09-01

    Full Text Available Oligoetherols based on pyrimidine ring were obtained upon reaction of barbituric acid with glycidol and alkylene carbonates. These oligoetherols were then used to obtain polyurethane foams in the reaction of oligoetherols with isocyanates and water. The protocol of foam synthesis was optimized by the choice of proper kind of oligoetherol and synthetic composition. The thermal resistance was studied by dynamic and static methods with concomitant monitoring of compressive strength. The polyurethane foams have similar physical properties as the classic ones except their enhanced thermal resistance. They stand long-time heating even at 200°C. Moreover thermal exposition of foams results generally in increase of their compressive strength.

  12. Polysubstituted pyrimidines: biological and chemical properties

    Janeba, Zlatko

    Santa Barbara: International Society of Heterocyclic Chemistry, 2015. 0073. [International Society of Heterocyclic Chemistry Congress /25./. 23.08.2015-28.08.2015, Santa Barbara] R&D Projects: GA MV VG20102015046; GA ČR GA15-11223S Institutional support: RVO:61388963 Keywords : pyrimidine * intramolecular hydrogen bonding * planamerism Subject RIV: CC - Organic Chemistry

  13. Enzymology of Pyrimidine Metabolism and Neurodegeneration.

    Vincenzetti, Silvia; Polzonetti, Valeria; Micozzi, Daniela; Pucciarelli, Stefania

    2016-01-01

    It is well known that disorders of pyrimidine pathways may lead to neurological, hematological, immunological diseases, renal impairments, and association with malignancies. Nucleotide homeostasis depends on the three stages of pyrimidine metabolism: de novo synthesis, catabolism and recycling of these metabolites. Cytidine and uridine, in addition to be used as substrates for pyrimidine nucleotide salvaging, also act as the precursors of cytidine triphosphate used in the biosynthetic pathway of both brain's phosphatidylcholine and phosphatidylethanolamine via the Kennedy cycle. The synthesis in the brain of phosphatidylcholine and other membrane phosphatides can utilize, in addition to glucose, three compounds present in the blood stream: choline, uridine, and a polyunsaturated fatty acids like docosahexaenoic acid. Some authors, using rat models, found that oral administration of two phospholipid precursors such as uridine and omega-3 fatty acids, along with choline from the diet, can increase the amount of synaptic membrane generated by surviving striatal neurons in rats with induced Parkinson's disease. Other authors found that in hypertensive rat fed with uridine and choline, cognitive deficit resulted improved. Uridine has also been recently considered as a neuroactive molecule, because of its involvement in important neurological functions by improving memory, sleep disorders, anti-epileptic effects, as well as neuronal plasticity. Cytidine and uridine are uptaken by the brain via specific receptors and successively salvaged to the corresponding nucleotides. The present review is devoted to the enzymology of pyrimidine pathways whose importance has attracted the attention of several researchers investigating on the mechanisms underlying the physiopathology of brain. PMID:27063261

  14. Genetic factors influencing pyrimidine-antagonist chemotherapy

    Maring, JG; Groen, HJM; Wachters, FM; Uges, DRA; de Vries, EGE

    2005-01-01

    Pyrimidine antagonists, for example, 5-fluorouracil (5-FU), cytarabine (ara-C) and gemcitabine (dFdC), are widely used in chemotherapy regimes for colorectal, breast, head and neck, non-small-cell lung cancer, pancreatic cancer and leukaemias. Extensive metabolism is a prerequisite for conversion of

  15. Novel Lipid-Soluble Thiol-Redox Antioxidant and Heavy Metal Chelator, N,N′-bis(2-Mercaptoethyl)Isophthalamide (NBMI) and Phospholipase D-Specific Inhibitor, 5-Fluoro-2-Indolyl Des-Chlorohalopemide (FIPI) Attenuate Mercury-Induced Lipid Signaling Leading to Protection Against Cytotoxicity in Aortic Endothelial Cells

    Secor, Jordan D.; Kotha, Sainath R.; Gurney, Travis O.; Patel, Rishi B.; Kefauver, Nicholas R.; Gupta, Niladri; Morris, Andrew J.; Haley, Boyd E.; Parinandi, Narasimham L.

    2011-01-01

    Here, we investigated thiol-redox-mediated phospholipase D (PLD) signaling as a mechanism of mercury cytotoxicity in mouse aortic endothelial cell (MAEC) in vitro model utilizing the novel lipid-soluble thiol-redox antioxidant and heavy metal chelator, N,N′-bis(2-mercaptoethyl)isophthalamide (NBMI) and the novel PLD-specific inhibitor, 5-fluoro-2-indolyl des-chlorohalopemide (FIPI). Our results demonstrated (i) mercury in the form of mercury(II) chloride, methylmercury, and thimerosal induced...

  16. Repair of DNA-containing pyrimidine dimers

    Ultraviolet light-induced pyrimidine dimers in DNA are recognized and repaired by a number of unique cellular surveillance systems. The most direct biochemical mechanism responding to this kind of genotoxicity involves direct photoreversal by flavin enzymes that specifically monomerize pyrimidine:pyrimidine dimers monophotonically in the presence of visible light. Incision reactions are catalyzed by a combined pyrimidine dimer DNA-glycosylase:apyrimidinic endonuclease found in some highly UV-resistant organisms. At a higher level of complexity, Escherichia coli has a uvr DNA repair system comprising the UvrA, UvrB, and UvrC proteins responsible for incision. There are several preincision steps governed by this pathway, which includes an ATP-dependent UvrA dimerization reaction required for UvrAB nucleoprotein formation. This complex formation driven by ATP binding is associated with localized topological unwinding of DNA. This same protein complex can catalyze an ATPase-dependent 5'----3'-directed strand displacement of D-loop DNA or short single strands annealed to a single-stranded circular or linear DNA. This putative translocational process is arrested when damaged sites are encountered. The complex is now primed for dual incision catalyzed by UvrC. The remainder of the repair process involves UvrD (helicase II) and DNA polymerase I for a coordinately controlled excision-resynthesis step accompanied by UvrABC turnover. Furthermore, it is proposed that levels of repair proteins can be regulated by proteolysis. UvrB is converted to truncated UvrB* by a stress-induced protease that also acts at similar sites on the E. coli Ada protein. Although UvrB* can bind with UvrA to DNA, it cannot participate in helicase or incision reactions. It is also a DNA-dependent ATPase.21 references

  17. Repair of DNA-containing pyrimidine dimers

    Grossman, L.; Caron, P.R.; Mazur, S.J.; Oh, E.Y.

    1988-08-01

    Ultraviolet light-induced pyrimidine dimers in DNA are recognized and repaired by a number of unique cellular surveillance systems. The most direct biochemical mechanism responding to this kind of genotoxicity involves direct photoreversal by flavin enzymes that specifically monomerize pyrimidine:pyrimidine dimers monophotonically in the presence of visible light. Incision reactions are catalyzed by a combined pyrimidine dimer DNA-glycosylase:apyrimidinic endonuclease found in some highly UV-resistant organisms. At a higher level of complexity, Escherichia coli has a uvr DNA repair system comprising the UvrA, UvrB, and UvrC proteins responsible for incision. There are several preincision steps governed by this pathway, which includes an ATP-dependent UvrA dimerization reaction required for UvrAB nucleoprotein formation. This complex formation driven by ATP binding is associated with localized topological unwinding of DNA. This same protein complex can catalyze an ATPase-dependent 5'----3'-directed strand displacement of D-loop DNA or short single strands annealed to a single-stranded circular or linear DNA. This putative translocational process is arrested when damaged sites are encountered. The complex is now primed for dual incision catalyzed by UvrC. The remainder of the repair process involves UvrD (helicase II) and DNA polymerase I for a coordinately controlled excision-resynthesis step accompanied by UvrABC turnover. Furthermore, it is proposed that levels of repair proteins can be regulated by proteolysis. UvrB is converted to truncated UvrB* by a stress-induced protease that also acts at similar sites on the E. coli Ada protein. Although UvrB* can bind with UvrA to DNA, it cannot participate in helicase or incision reactions. It is also a DNA-dependent ATPase.21 references.

  18. Triplex-induced recombination and repair in the pyrimidine motif

    Kalish, Jennifer M.; Seidman, Michael M.; Weeks, Daniel L.; Glazer, Peter M.

    2005-01-01

    Triplex-forming oligonucleotides (TFOs) bind DNA in a sequence-specific manner at polypurine/polypyrimidine sites and mediate targeted genome modification. Triplexes are formed by either pyrimidine TFOs, which bind parallel to the purine strand of the duplex (pyrimidine, parallel motif), or purine TFOs, which bind in an anti-parallel orientation (purine, anti-parallel motif). Both purine and pyrimidine TFOs, when linked to psoralen, have been shown to direct psoralen adduct formation in cells...

  19. Fluorine-18 labeled tetrahydrocannabinol: Synthesis and PET studies in a boron

    Cannabinoids, the active components of marijuana are known to be psychotic. The most active components of this class of compound are delta-9-tetrahydrocannabinol (Δ9-THC) and its delta-8 isomer. While Δ8-THC and Δ9-THC have similar psychotic activity, Δ8-THC is more stable than its Δ9 analog. Recently, several cannabinoids are found to have high binding affinity to the brain. However, little is known about the mechanisms of their actions. In order to study its pharmacokinetic in animals, the authors have synthesized fluorine-18 labeled 5'-fluoro-Δ8-THC and studied its distribution in mice and in a baboon brain

  20. Indolizines and pyrrolo[1,2-c]pyrimidines decorated with a pyrimidine and a pyridine unit respectively

    Georgescu, Emilian; Georgescu, Florentina; Draghici, Constantin; Stan, Raluca; Deleanu, Calin; Dumitrascu, Florea

    2015-01-01

    Summary The three possible structural isomers of 4-(pyridyl)pyrimidine were employed for the synthesis of new pyrrolo[1,2-c]pyrimidines and new indolizines, by 1,3-dipolar cycloaddition reaction of their corresponding N-ylides generated in situ from their corresponding cycloimmonium bromides. In the case of 4-(3-pyridyl)pyrimidine and 4-(4-pyridyl)pyrimidine the quaternization reactions occur as expected at the pyridine nitrogen atom leading to pyridinium bromides and consequently to new indolizines via the corresponding pyridinium N-ylides. However, in the case of 4-(2-pyridyl)pyrimidine the steric hindrance directs the reaction to the pyrimidinium N-ylides and, subsequently, to the formation of the pyrrolo[1,2-c]pyrimidines. The new pyrrolo[1,2-c]pyrimidines and the new indolizines were structurally characterized through NMR spectroscopy. The X-ray structures of two of the starting materials, 4-(2-pyridyl)pyrimidine and 4-(4-pyridyl)pyrimidine, are also reported. PMID:26199663

  1. Indolizines and pyrrolo[1,2-c]pyrimidines decorated with a pyrimidine and a pyridine unit respectively.

    Popa, Marcel Mirel; Georgescu, Emilian; Caira, Mino R; Georgescu, Florentina; Draghici, Constantin; Stan, Raluca; Deleanu, Calin; Dumitrascu, Florea

    2015-01-01

    The three possible structural isomers of 4-(pyridyl)pyrimidine were employed for the synthesis of new pyrrolo[1,2-c]pyrimidines and new indolizines, by 1,3-dipolar cycloaddition reaction of their corresponding N-ylides generated in situ from their corresponding cycloimmonium bromides. In the case of 4-(3-pyridyl)pyrimidine and 4-(4-pyridyl)pyrimidine the quaternization reactions occur as expected at the pyridine nitrogen atom leading to pyridinium bromides and consequently to new indolizines via the corresponding pyridinium N-ylides. However, in the case of 4-(2-pyridyl)pyrimidine the steric hindrance directs the reaction to the pyrimidinium N-ylides and, subsequently, to the formation of the pyrrolo[1,2-c]pyrimidines. The new pyrrolo[1,2-c]pyrimidines and the new indolizines were structurally characterized through NMR spectroscopy. The X-ray structures of two of the starting materials, 4-(2-pyridyl)pyrimidine and 4-(4-pyridyl)pyrimidine, are also reported. PMID:26199663

  2. The Synthesis and Structure-identification of 2-Benzyloxy-5-fluoro-4-oxo-pyrimidine-3-butyric Acid Ethyl Ester%2-苄氧基-5-氟-4-嘧啶酮-3-丁酸乙酯的合成及结构鉴定

    谢珺; 张旭; 王建塔; 汤磊

    2006-01-01

    目的: 合成氟尿嘧啶类衍生物合成中的关键中间体2-苄氧基-5-氟-4-嘧啶酮-3-丁酸乙酯.方法: 以5-氟尿嘧啶为原料, 经4步反应合成目标产物,并用红外光谱(IR)、核磁共振(1H-NMR)进行了结构确证.结果: 2-苄氧基-5-氟-4-嘧啶酮和γ-溴代丁酸乙酯反应得到两个化合物.结论: 通过IR谱确证一个化合物是目标物2-苄氧基-5-氟-4-嘧啶酮-3-丁酸乙酯,另一化合物是它的同分异构体.

  3. Synthetic strategies toward carbocyclic purine-pyrimidine hybrid nucleosides.

    Sadler, Joshua M; Mosley, Sylvester L; Dorgan, Kathleen M; Zhou, Zhaohui Sunny; Seley-Radtke, Katherine L

    2009-08-01

    The blending of key structural features from the purine and pyrimidine nucleobase scaffolds gives rise to a new class of hybrid nucleosides. The purine-pyrimidine hybrid nucleosides can be viewed as either N-3 ribosylated purines or 5,6-disubstituted pyrimidines, thus recognition by both purine- and pyrimidine-metabolizing enzymes is possible. Given the increasing reports of the development of resistance in many enzymatic systems, a drug that could be recognized by more than one enzyme could prove highly advantageous in overcoming resistance mechanisms related to binding site mutations. In that regard, the design, synthesis and results of preliminary biological activity for a series of carbocyclic uracil derivatives with either a fused imidazole or thiazole ring are presented herein. PMID:19592260

  4. Synthesis of novel chiral compounds of purine and pyrimidine bases

    汪毓海; 陈庆华

    1999-01-01

    The physiologically active groups such as purine and pyrimidine bases are introduced to the asymmetric ynthesis. The optically pure compounds bearing purine and pyrimidine bases (5a—5e) were prepared via the asymetric Michael addition reaction of purines and pyrimidines as Michael donators with the chiral source 5-(R)-[(1R, 2S, 5R)-menthyloxy]-2(5H)-furanone (3a), which was prepared from the natural chiral auxiliary (-)-menthol. The synthetic method was studied in detail and the new compounds were identified on the basis of their analytical data and spectroscopic data, such as [α]D20, IR, UV, 1H NMR, 13C NMR and MS. The absolute configuration of 5a was established by X-ray crystallography. The results provided an efficient synthetic route to chiral purines and pyrimidine analogues, and offered chiral sources for further research on the physiologically active compounds of chiral nucleotides.

  5. Pyrimidine analogues as prospective anti-inflammatory compounds

    Zídek, Zdeněk; Jansa, Petr; Janeba, Zlatko; Kostecká, Petra; Kmoníčková, Eva

    Košice: -, 2012. s. 59-59. [Farmakologické dni /62./. 25.06.2012-27.06.2012, Košice] Institutional support: RVO:61388963 ; RVO:68378041 Keywords : pyrimidine Subject RIV: FR - Pharmacology ; Medidal Chemistry

  6. The solid-state synthesis of tritium labelled heterocyclic bases

    Sidorov, G.V.; Myasoedov, N.F. (AN SSSR, Moscow (Russian Federation). Inst. Molekulyarnoj Genetiki)

    1994-04-01

    The results of a study of the solid-state catalytic hydrogenation and the synthesis of tritium labelled native heterocyclic bases are presented. The effect of different palladium catalysts and reaction conditions on yield and molar radioactivity of final compounds was investigated. For some compounds, data on the intramolecular distribution of tritium were obtained by using the isotope exchange reaction and tritium NMR. Tritium labelled purine and pyrimidine bases (25-180 Ci/mmol.) were synthesized. (Author).

  7. Pyrimidine metabolism of Bdellovibrio bacteriovorus grown intraperiplasmically and axenically.

    Rosson, R A; Rittenberg, S C

    1981-01-01

    Bdellovibrio bacteriovorus grown axenically or intraperiplasmically on Escherichia coli has pathways for the interconversion of pyrimidines and the synthesis of pyrimidine nucleoside 5'-triphosphates similar to those found in the enteric bacteria. Minimal differences in enzyme activities were observed for axenically and intraperiplasmically grown cells. As might be expected for an organism which takes up deoxyribonucleoside 5'-monophosphates per se, high levels of enzymes which catalyze the g...

  8. Low-energy positron scattering by pyrimidine

    Barbosa, Alessandra Souza; Pastega, Diego F.; Bettega, Márcio H. F., E-mail: bettega@fisica.ufpr.br [Departamento de Física, Universidade Federal do Paraná, Caixa Postal 19044, 81531-990 Curitiba, Paraná (Brazil)

    2015-12-28

    This work reports elastic integral and differential cross sections for positron collisions with pyrimidine, for energies up to 20 eV. The cross sections were computed with the Schwinger multichannel method in the static plus polarization approximation. We also employed the Born closure procedure to account for the long range potential due to the permanent dipole moment of the molecule. Our results are compared with the experimental total cross section of Zecca et al. [J. Phys. B 43, 215204 (2010)], the experimental grand-total, quasi-elastic integral and differential cross section of Palihawadana et al. [Phys. Rev. A 88, 12717 (2013)]. We also compare our results with theoretical integral and differential cross sections obtained by Sanz et al. [Phys. Rev. A 88, 62704 (2013)] with the R-matrix and the independent atom model with screening-corrected additivity rule methods, and with the results computed by Franz and Gianturco [Phys. Rev. A 88, 042711 (2013)] using model correlation-polarization potentials. The agreement between the theory and the experiment is encouraging.

  9. Synthesis of Some New Condensed Pyrimidine Derivatives

    Cyclodehydration of 6-amino-5-cyano pyrimidine derivative (2) afforded pyrimidoisoindole derivatives (3). Compound (3) reacted with carbethoxymethylene derivative to give pyridopyrimidine derivatives (5a,b). Compound (3) was also reacted with formamide to give the corresponding pyrimidopyrimdine derivatives (6) that condensed with benzaldehyde to give Schiff's base (7). Refluxing of compound (3) with triethyl orthoformate afforded compound (8) that cyclized with ammonium hydroxide giving the same compound (6). Compound (8) cyclized with hydrazine hydrate giving compound (9) which also cyclized with triethyl orthoformate affording compound (10). Diazotization of compound (3) led to the formation of triazinopyrimidine derivative (11). Cyclization of compound (11) upon treatment with hydrazine hydrate afforded compound (12). Compound (15) was prepared from reaction of compound (3) and ethylenediamine in presence of carbon disulfide. The behaviour of compound (15) toward benzoyl chloride, triethyl orthoformate, nitrous acid and/or carbon disulfide was also described. All proposed structures were supported by elemental analyses, spectroscopic data and some of the new products showed antimicrobial activity

  10. Purine and pyrimidine nucleotide metabolism in Mollicutes

    Cristiano Valim Bizarro

    2007-01-01

    Full Text Available Several mollicute genome projects are underway, offering unique opportunities to study genes and metabolic pathways on a genome-wide scale. Here, we have analyzed the conservation and diversity of purine and pyrimidine metabolism in mycoplasmas. An evaluation of discrepancies between genomic analysis and enzymatic data revealed interesting aspects about these organisms. We found important examples in which enzyme activity was reported without the annotation of a corresponding gene. An interesting example concerns phosphopentomutase. In Mollicutes, we have identified CDSs orthologous to sequences recently identified as new phosphopentomutases in archaeobacteria that are structurally related to phosphomannomutases. It is suggested that these sequences could replace the function of phosphopentomutases in mollicutes lacking the canonical phosphopentomutase gene (deoB. Also, the activity of 5'-nucleotidase was reported in mollicutes that do not possess any CDS related to ushA. Hypothetical proteins exhibiting domains similar to newly characterized 5' nucleotidases in Escherichia coli are proposed as possible CDSs related to this enzymatic activity in Mollicutes. Based on our analysis, the reductive genome evolution of Mollicutes does not appear to result in a minimum set of genes nor a minimum set of metabolic functions shared by all mollicute species.

  11. Topical formulation engendered alteration in p53 and cyclobutane pyrimidine dimer expression in chronic photodamaged patients.

    Spencer, James M; Morgan, Michael B; Trapp, Kara M; Moon, Summer D

    2013-03-01

    While the clinical attributes of photoaging are well characterized in the literature, the pathogenic mechanisms that underlie these changes are incompletely elucidated. At the molecular level, p53 tumor-suppressor gene product mediated excision repair of ultraviolet (UV)-induced DNA damage is a critical effector in xeroderma pigmentosum (XP) and potentially in conventional photoaging. We examined p53 activity and measured UV-induced DNA damage via cyclobutane pyrimidine dimers (CPDs) quantitatively in 20 volunteers before and after an 8-week, open-label prospective topical application of a proprietary DNA recovery serum (Celfix). There was a statistically significant decrease in immunohistochemically determined p53 and CPD levels. While these data are preliminary, the findings lend support to the theoretical possibility of a topical agent reversing the effects of photodamage at the molecular level and, potentially, an ameliorative outcome clinically. PMID:23545918

  12. Strains of Lactococcus lactis with a partial pyrimidine requirement show sensitivity toward aspartic acid

    Wadskov-Hansen, Steen Lyders Lerche; Martinussen, Jan

    2009-01-01

    that the partial pyrimidine requirement can be explained by a low specific activity of the pyrimidine biosynthetic enzymes. In conclusion, L. lactis LM0230 during the process of plasmid- and prophage-curing has acquired a partial pyrimidine requirement resulting in sensitivity toward aspartic acid....

  13. Structure-activity-relationships (SAR) in pyrimidine nucleoside transport

    Several series of pyrimidine nucleosides were evaluated as part of a larger program to develop non-invasive brain imaging agents. The interaction of these antitumor/antiviral nucleosides with an NBMPR-sensitive murine erythroctye nucleoside transporter was evaluated by determining their inhibitory effect (Ki) on zero-trans influx of thymidine. Within each series of compounds, which had F, Cl, Br or I as halogen substituents, an increase in size of the halogen atom or a decrease in electronegativity decreased affinity for the transporter. Partition coefficients (P) of these pyrimidine nucleosides were measured to determine their potential to diffuse across the blood-brain-barrier (BBB). Most of the pyrimidine nucleosides had lower P values (log P i for nucleosides with a particular sugar moiety. Within a nucleoside series with a given sugar component, the binding affinity for the transporter was inversely proportional to lipophilicity. 25 refs., 2 tabs., 4 figs

  14. Significance and Biological Importance of Pyrimidine in the Microbial World

    Vinita Sharma

    2014-01-01

    Full Text Available Microbes are unique creatures that adapt to varying lifestyles and environment resistance in extreme or adverse conditions. The genetic architecture of microbe may bear a significant signature not only in the sequences position, but also in the lifestyle to which it is adapted. It becomes a challenge for the society to find new chemical entities which can treat microbial infections. The present review aims to focus on account of important chemical moiety, that is, pyrimidine and its various derivatives as antimicrobial agents. In the current studies we represent more than 200 pyrimidines as antimicrobial agents with different mono-, di-, tri-, and tetrasubstituted classes along with in vitro antimicrobial activities of pyrimidines derivatives which can facilitate the development of more potent and effective antimicrobial agents.

  15. Food Labels

    ... How Can I Help a Friend Who Cuts? Food Labels KidsHealth > For Teens > Food Labels Print A ... have at least 95% organic ingredients. continue Making Food Labels Work for You The first step in ...

  16. 5-(2-amimo-4-styryl pyrimidine-4-yl-4-methoxybenzofuran-6-ol

    Atteyat A Labib

    2013-05-01

    Full Text Available This study describes the organic synthesis of 5-(2-amimo-4-styryl pyrimidine-4-yl-4-methoxy benzofuran-6-ol (SPBF as an example of a benzofuran derivative used as a new series of amyloid imaging agents. These benzofuran derivatives may be useful amyloid imaging agents for detecting B-amyloid plagues in the brain of Alzheimer’s disease. The precursor is 1-[6-hydroxy-4-methoxybenzofuran-5-yl]-phenyl butadiene ketone, which react with guanidine hydrochloride. The purification process was done via crystallization using solvent ethanol. The overall yield was 75% and the structure of the synthesized compound was confirmed by correct analytical and spectral data. Also, The synthesized compound was labeled with radioactive iodine -125 via electrophilic substitution reaction, in the presence of iodogen as an oxidizing agent, the labeling process was carried out at 95oC for 20min. The radiochemical yield was determined by using a thin layer chromatography and the yield was equal to 80%. Preliminary an in-vivo study examined normal mice after intravenous injection through the tail vein and the data showed the labeling compound was quickly cleared from most body organs. The radioiodinated compound showed high brain uptake.The results of this study suggest that radioiodinated (SPBF may be useful as a brain imaging agents.

  17. Carbocyclic pyrimidine nucleosides as inhibitors of S-adenosylhomocysteine hydrolase.

    Mosley, Sylvester L; Bakke, Brian A; Sadler, Joshua M; Sunkara, Naresh K; Dorgan, Kathleen M; Zhou, Zhaohui Sunny; Seley-Radtke, Katherine L

    2006-12-01

    The design, synthesis, and unexpected inhibitory activity against S-adenosyl-homocysteine (SAH) hydrolase (SAHase, EC 3.3.1.1) for a series of truncated carbocyclic pyrimidine nucleoside analogues is presented. Of the four nucleosides obtained, 10 was found to be active with a Ki value of 5.0 microM against SAHase. PMID:16904326

  18. Nucleotide metabolism in Lactococcus lactis: Salvage pathways of exogenous pyrimidines

    Martinussen, Jan; Andersen, Paal Skytt; Hammer, Karin

    1994-01-01

    By measuring enzyme activities in crude extracts and studying the effect of toxic analogs (5-fluoropyrimidines) on cell growth, the metabolism of pyrimidines in Lactococcus lactis was analyzed. Pathways by which uracil, uridine, deoxyuridine, cytidine, and deoxycytidine are metabolized in L. lact...

  19. Inhibition of semiconservative DNA synthesis in ICR 2A frog cells by pyrimidine dimers and nondimer photoproducts induced by ultraviolet radiation

    DNA synthesis was examined in ultraviolet (uv)-irradiated ICR 2A frog cells in which either pyrimidine dimers or nondimer photoproducts represented the major class of DNA lesions. In addition, cells were exposed to 60Co γ rays. The cultures were pulse-labeled and the size distribution of the DNA synthesized was estimated using both sucrose gradient sedimentation and alkaline step elution. Using either of these techniques, it was found that the presence of dimers resulted in a reduction principally in the synthesis of high molecular weight (MW) DNA. In contrast, nondimer photoproducts caused a strong inhibition in the synthesis of low MW DNA, as was also observed in γ-irradiated cells. Hence the induction of pyrimidine dimers in DNA mainly affected the elongation of replicons, whereas nondimer lesions primarily caused an inhibition of replicon initiation

  20. Annellation of Triazole and Tetrazole Systems onto Pyrrolo[2,3-d]pyrimidines: Synthesis of Tetrazolo[1,5-c]-pyrrolo[3,2-e]-pyrimidines and Triazolo[1,5-c]pyrrolo-[3,2-e]pyrimidines as Potential Antibacterial Agents

    Rina D. Shah

    2002-07-01

    Full Text Available Syntheses of several novel 4-chloropyrrolo[2,3-d]pyrimidines (1, 4-hydrazinopyrrolo[2,3-d]pyrimidines (2 and 3-amino-4-iminopyrrolo[2,3-d]pyrimidines (7 and their use in the synthesis of tetrazolo[1,5-c]pyrrolo[3,2-e]pyrimidines (3 and triazolo[1,5-c]pyrrolo[3,2-e]pyrimidines (4 required for biological screening are reported.

  1. A novel and convenient synthesis of thiazolo[3,2-a]pyrimidin-7-ones and pyrido[1,2-a]pyrimidin-2-ones using Vilsmeier reagent

    Yi Yi Weng; Lei Ming Ying; Qi Xu Chen; Wei Ke Su

    2012-01-01

    A novel route for the synthesis of thiazolo[3,2-a]pyrimidin-7-ones and pyrido[1,2-a]pyrimidin-2-ones from acetylated 2-aminothiazoles and 2-aminopyridines under Vilsmeier conditions has been developed.The plausible mechanism has also been proposed.

  2. Photochemical labeling of bovine pancreatic ribonuclease A with 8-azidoadenosine 3',5'-bisphosphate

    A simple method has been developed for the preparation of 5'-32P-labeled 8-azidoadenosine 3',5'-bisphosphate (p8N3Ap) for use in photoaffinity labeling studies. Irradiation of a complex between p8N3Ap and bovine pancreatic ribonuclease A (RNase A) with light of 300-350 nm led to the covalent attachment of the nucleotide to the enzyme. RNase A could also be labeled in the dark with prephotolyzed p8N3Ap. In either case, the nucleotide reacted with the same tryptic peptide, encompassing amino acids 67-85 of the protein. The site of labeling was determined to be either Thr-78 or Thr-82, both of which are close to or at the pyrimidine binding site of the enzyme. This result is consistent with recent nuclear magnetic resonance and X-ray studies which indicate that 8-substituted adenine nucleotides interact with the pyrimidine binding site of RNase A

  3. Wasteful Labeling

    Mahenc, Philippe

    2009-01-01

    The role of labeling is to solve the adverse selection problem caused by unsubstantiated claims from firms. The problem however is likely to remain unsolved if the labeling agency is not trustworthy.The agency can be suspected to divert the fees charged for labeling from their primary purpose of collecting information in order to raise excessive revenue. This paper addresses this issue and shows that labeling may be wasteful if the agency is likely to be untrustworthy. To award firms green la...

  4. Electron- and proton-induced ionization of pyrimidine

    The present work describes a quantum-mechanically based model of the electron- and proton-induced ionization of isolated pyrimidine molecules. The impact energies range from the target ionization threshold up to ∼ 1 keV for electrons and from 10 keV up to 10 MeV for protons. The cross-section calculations are performed within the first Born approximation in which the ejected electron is described by a Coulomb wave whereas the incident and the scattered projectiles are both described by plane waves. The pyrimidine target is described using the Gaussian 09 software package. The theoretical predictions obtained are in good agreement with experimental absolute total cross sections, while large discrepancies are observed between existing semi-empirical models and the present calculations. (authors)

  5. Synthesis pharmacological evaluation and docking studies of pyrimidine derivatives.

    Giles, D; Roopa, Karki; Sheeba, F R; Gurubasavarajaswamy, P M; Divakar, Goli; Vidhya, Thomas

    2012-12-01

    A new group of pyrimidine derivatives of indane-1,3-dione were synthesized aiming at the synthesis of new compounds acting as analgesic, anti-inflammatory and antimicrobial activity in a single component. The title compounds (3a-l) were synthesized from chalcone derivatives of indane-1,3-dione (2a-l) through cyclization reaction with urea. The synthesized compounds were characterized by FT-IR, (1)H NMR, mass spectral data, elemental analysis and evaluated for anti-inflammatory, analgesic, antibacterial and antifungal activities. The most active compound 3e, was evaluated for its ulcerogenicity. Good anti-inflammatory property was observed for chlorophenyl substituted pyrimidine derivatives. It mainly binds with Pro 218 of 1CX2, and the ligand could have caused much conformational changes in the protein structure than other derivatives. It also exhibits good analgesic and antimicrobial agent in a single component. PMID:23159805

  6. Unanticipated role of melanin in causing carcinogenic cyclobutane pyrimidine dimmers

    Premi, Sanjay; Brash, Douglas E.

    2015-01-01

    Ultraviolet radiation (UVR) instantaneously generates cyclobutane pyrimidine dimers (CPDs). Paradoxically, we recently observed that UV enables the protective pigment melanin to create CPDs in the dark long after the exposure ends. UV-induced reactive oxygen species (ROS) oxidize melanin to create melanin carbonyls in a high-energy quantum state. These energetic melanin carbonyls transfer their energy to DNA in the dark, creating CPDs in the absence of UVR.

  7. Unanticipated role of melanin in causing carcinogenic cyclobutane pyrimidine dimmers.

    Premi, Sanjay; Brash, Douglas E

    2016-01-01

    Ultraviolet radiation (UVR) instantaneously generates cyclobutane pyrimidine dimers (CPDs). Paradoxically, we recently observed that UV enables the protective pigment melanin to create CPDs in the dark long after the exposure ends. UV-induced reactive oxygen species (ROS) oxidize melanin to create melanin carbonyls in a high-energy quantum state. These energetic melanin carbonyls transfer their energy to DNA in the dark, creating CPDs in the absence of UVR. PMID:27308551

  8. Inhibition of dengue virus through suppression of host pyrimidine biosynthesis.

    Wang, Qing-Yin; Bushell, Simon; Qing, Min; Xu, Hao Ying; Bonavia, Aurelio; Nunes, Sandra; Zhou, Jing; Poh, Mee Kian; Florez de Sessions, Paola; Niyomrattanakit, Pornwaratt; Dong, Hongping; Hoffmaster, Keith; Goh, Anne; Nilar, Shahul; Schul, Wouter; Jones, Susan; Kramer, Laura; Compton, Teresa; Shi, Pei-Yong

    2011-07-01

    Viral replication relies on the host to supply nucleosides. Host enzymes involved in nucleoside biosynthesis are potential targets for antiviral development. Ribavirin (a known antiviral drug) is such an inhibitor that suppresses guanine biosynthesis; depletion of the intracellular GTP pool was shown to be the major mechanism to inhibit flavivirus. Along similar lines, inhibitors of the pyrimidine biosynthesis pathway could be targeted for potential antiviral development. Here we report on a novel antiviral compound (NITD-982) that inhibits host dihydroorotate dehydrogenase (DHODH), an enzyme required for pyrimidine biosynthesis. The inhibitor was identified through screening 1.8 million compounds using a dengue virus (DENV) infection assay. The compound contains an isoxazole-pyrazole core structure, and it inhibited DENV with a 50% effective concentration (EC(50)) of 2.4 nM and a 50% cytotoxic concentration (CC(50)) of >5 μM. NITD-982 has a broad antiviral spectrum, inhibiting both flaviviruses and nonflaviviruses with nanomolar EC(90)s. We also show that (i) the compound inhibited the enzymatic activity of recombinant DHODH, (ii) an NITD-982 analogue directly bound to the DHODH protein, (iii) supplementing the culture medium with uridine reversed the compound-mediated antiviral activity, and (iv) DENV type 2 (DENV-2) variants resistant to brequinar (a known DHODH inhibitor) were cross resistant to NITD-982. Collectively, the results demonstrate that the compound inhibits DENV through depleting the intracellular pyrimidine pool. In contrast to the in vitro potency, the compound did not show any efficacy in the DENV-AG129 mouse model. The lack of in vivo efficacy is likely due to the exogenous uptake of pyrimidine from the diet or to a high plasma protein-binding activity of the current compound. PMID:21507975

  9. Study of [18F]FLT and [123I]IaraU for cellular imaging in HSV1 tk-transfected murine fibrosarcoma cells: evaluation of the tracer uptake using 5-fluoro, 5-iodo and 5-iodovinyl arabinosyl uridines as competitive probes

    As one of the most intensively studied probes for imaging of the cellular proliferation, [18F]FLT was investigated whether the targeting specificity of thymidine kinase 1 (TK1) dependency could be enhanced through a synergistic effect mediated by herpes simplex type 1 virus (HSV1) tk gene in terms of the TK1 or TK2 expression. 5-[123I]Iodo arabinosyl uridine ([123I]IaraU) was prepared in a radiochemical yield of 8% and specific activity of 21 GBq/μmol, respectively. Inhibition of the cellular uptake of these two tracers was compared by using the arabinosyl uridine analogs such as 5-iodo, 5-fluoro and 5-(E)-iodovinyl arabinosyl uridine along with 2′-fluoro-5-iodo arabinosyl uridine (FIAU). Due to potential instability of the iodo group, accumulation index of 1.6 for [123I]IaraU by HSV1-TK vs. control cells could virtually be achieved at 1.5 h, but dropped to 0.2 compared to 2.0 for [18F]FLT at 5 h. The results from competitive inhibition by these nucleosides against the accumulation of [18F]FLT implied that FLT exerted a mixed TK1- and TK2-dependent inhibition with HSV1-tk gene transfection because of the shifting of thymidine kinase status. Taken together, the combination of [18F]FLT and HSV1-TK provides a synergistic imaging potency.

  10. 2-Alkyl-4-aryl-pyrimidine fused heterocycles as selective 5-HT2A antagonists.

    Shireman, Brock T; Dvorak, Curt A; Rudolph, Dale A; Bonaventure, Pascal; Nepomuceno, Diane; Dvorak, Lisa; Miller, Kirsten L; Lovenberg, Timothy W; Carruthers, Nicholas I

    2008-03-15

    The synthesis and SAR for a novel series of 2-alkyl-4-aryl-tetrahydro-pyrido-pyrimidines and 2-alkyl-4-aryl-tetrahydro-pyrimido-azepines is described. Representative compounds were shown to be subtype selective 5-HT(2A) antagonists. Optimal placement of a basic nitrogen relative to the pyrimidine and the presence of a 4-fluorophenyl group in the pyrimidine 4-position was found to have a profound effect on affinity and selectivity. PMID:18282705

  11. Nutrition Labeling

    Grunert, Klaus G

    2013-01-01

    because consumers will avoid products that the label shows to be nutritionally deficient, but also because food producers will try to avoid marketing products that appear, according to the label, as nutritionally problematic, for example, because of a high content of saturated fat or salt. Nutrition......Nutrition labeling refers to the provision of information on a food product’s nutritional content on the package label. It can serve both public health and commercial purposes. From a public health perspective, the aim of nutrition labeling is to provide information that can enable consumers...... to make healthier choices when choosing food products. Nutrition labeling is thus closely linked to the notion of the informed consumer, that chooses products according to their aims, on the basis of the information at their disposal. Because many consumers are assumed to be interested in making healthy...

  12. Nutrition Labeling

    Metzger, Lloyd E.

    Nutrition labeling regulations differ in countries around the world. The focus of this chapter is on nutrition labeling regulations in the USA, as specified by the Food and Drug Administration (FDA) and the Food Safety and Inspection Service (FSIS) of the United States Department of Agriculture (USDA). A major reason for analyzing the chemical components of foods in the USA is nutrition labeling regulations. Nutrition label information is not only legally required in many countries, but also is of increasing importance to consumers as they focus more on health and wellness.

  13. An efficient synthesis of pyrazolo[1,5-a]pyrimidines and evaluation of their antimicrobial activity

    SOMESHWAR DESHMUKH; KUNAL DINGORE; VISHWAS GAIKWAD; MADHUKAR JACHAK

    2016-09-01

    A series of new pyrazolo[1,5-a]pyrimidine derivatives has been synthesized by using 7-hydrazinyl- 5-methylpyrazolo[1,5-a]pyrimidine-3-carbonitrile 1 and 7-amino-5-methylpyrazolo[1,5-a]pyrimidine-3-carbonitrile 2 as precursors. The pyrazolo[3,4-d] pyrimidines 3a–b have been synthesized by a three-step reactionstarting with 1. Compound 1 was utilized for the synthesis of dioxopyrrolidindolinylamio-pyrazolo-pyrimidines 4a–b, and dioxoisoindolin-pyrazolo-pyrimidines 4c–d. Also, compounds 4a-d were synthesized using deepeutectic solvents (DES). This method using DES provides several advantages such as benign environment, high yield, scalable and simple work-up procedure. Similarly, the cyclocondensation of 2 with α-acetyl- γ -butyrolactone afforded pyrazolo-pyrido-pyrimidine 5 and dihydrofuro-pyrido-pyrazolo-pyrimidine 6. All synthesized compounds were screened for antimicrobial activity.

  14. Tetra-n-butylammonium Hydroxide: an Efficient Catalyst for N-Alkylation of Pyrimidines and Purines

    2006-01-01

    An efficient procedure for N-alkylation of pyrimidines and purines in the presence of tetra-n-butylammonium hydroxide(TBAH) is described. The method is very practical and the alkylation can occur at room temperature and the yields of the N-alkyl pyrimidines and purines were found to be excellent.

  15. Privileged substructure-based diversity-oriented synthesis pathway for diverse pyrimidine-embedded polyheterocycles

    Kim, Heejun; Thanh Tung, Truong; Park, Seung Bum

    2013-01-01

    A new diversity-oriented synthesis pathway for the fabrication of a pyrimidine-embedded polyheterocycles library was developed for potential interactions with diverse biopolymers. Five different pyrimidine-embedded core skeletons were synthesized from ortho-alkynylpyrimidine carbaldehydes by a...

  16. A second pathway to degrade pyrimidine nucleic acid precursors in eukaryotes

    Andersen, Gorm; Bjornberg, Olof; Polakova, Silvia;

    2008-01-01

    Pyrimidine bases are the central precursors for RNA and DNA, and their intracellular pools are determined by de novo, salvage and catabolic pathways. In eukaryotes, degradation of uracil has been believed to proceed only via the reduction to dihydrouracil. Using a yeast model, Saccharomyces kluyv...... of the eukaryotic or prokaryotic genes involved in pyrimidine degradation described to date....

  17. 2-(4-Bromophenyl-5-fluoro-3-phenylsulfinyl-1-benzofuran

    Hong Dae Choi

    2010-08-01

    Full Text Available In the title compound, C20H12BrFO2S, the O atom and the phenyl group of the phenylsulfinyl substituent lie on opposite sides of the plane through the benzofuran fragment; the phenyl ring is nearly perpendicular to this plane [dihedral angle = 86.98 (6°]. The 4-bromophenyl ring is rotated slightly out of the benzofuran plane, making a dihedral angle of 1.56 (8°. The crystal structure features aromatic π–π interactions between the furan and phenyl rings of neighbouring molecules [centroid–centroid distance = 3.506 (3 Å], and an intermolecular C—H...π interaction. The crystal structure also exhibits a short intermolecular S...S contact [3.2635 (8 Å].

  18. [2+2] Photocycloaddition reaction dynamics of triplet pyrimidines.

    Yang, Chunfan; Yu, Youqing; Liu, Kunhui; Song, Di; Wu, Lidan; Su, Hongmei

    2011-06-01

    Taking the 266 nm excited pyrimidine (uracil or thymine) with cyclopentene as model reaction systems, we have examined the photoproduct formation dynamics from the [2 + 2] photocycloaddition reactions of triplet pyrimidines in solution and provided mechanistic insights into this important DNA photodamage reaction. By combining two compliment methods of nanosecond time-resolved transient IR and UV-vis laser flash-photolysis spectroscopy, the photoproduct formation dynamics as well as the triplet quenching kinetics are measured. Characteristic IR absorption bands due to photoproduct formation have been observed and product quantum yields are determined to be ∼0.91% for uracil and ∼0.41% for thymine. Compared to the measured large quenching rate constants of triplet uracil (1.5 × 10(9) M(-1)s(-1)) or thymine (0.6 × 10(9) M(-1)s(-1)) by cyclopentene, the inefficiency in formation of photoproducts indicates competitive physical quenching processes may exist on the route leading to photoproducts, resulting in very small product yields eventually. Such an energy wasting process is found to be resulted from T(1)/S(0) surface crossings by the hybrid density functional calculations, which compliments the experiments and reveals the reaction mechanism. PMID:21557584

  19. 3-[(Furan-2-ylcarbonyl]-1-(pyrimidin-2-ylthiourea

    Durga P. Singh

    2012-12-01

    Full Text Available The title compound, C10H8N4O2S, was synthesized from furoyl isothiocynate and 2-aminopyrimidine in dry acetone. The two N—H groups are in an anti conformation with respect to each other and one N—H group is anti to the C=S group while the other is syn. The amide C=S and the C=O groups are syn to each other. The mean plane of the central thiourea fragment forms dihedral angles of 13.50 (14 and 5.03 (11° with the furan and pyrimidine rings, respectively. The dihedral angle between the furan and pyrimidine rings is 18.43 (10°. The molecular conformation is stabilized by an intramolecular N—H...N hydrogen bond generating an S(6 ring motif. In the crystal, molecules are linked by pairs of N—H...N and weak C—H...S hydrogen bonds to form inversion dimers.

  20. Soft functional polynuclear coordination compounds containing pyrimidine bridges

    Navarro, Jorge A. R.; Barea, Elisa; Galindo, Miguel A.; Salas, Juan M.; Romero, M. Angustias; Quirós, Miguel; Masciocchi, Norberto; Galli, Simona; Sironi, Angelo; Lippert, Bernhard

    2005-08-01

    In this account, we describe the use of simple pyrimidine derivatives in combination with metal ions to build highly structured molecular architectures containing functional nanoenvironments, cavities and surfaces that can interact with additional species. The supramolecular structure of these systems can be rationally controlled by metal fragment geometry, reaction conditions and presence of templating agents. Thus, the use of transition metals with low coordination numbers or blocked bonding positions in combination with pyrimidines (e.g. 2-hydroxypyrimidine, 4-hydroxypyrimidine, 2,4-dihydroxypyrimidine, 2-aminopyrimidine) leads to the formation of either discrete assemblies, 1D polymers or helixes. When metal ions with higher coordination possibilities are applied instead, 2D and 3D networks are generated. Some of the assemblies built in this way possess functional cavities, pores and surfaces that can interact with additional species by means of hydrophobic, electrostatic, H-bonding interactions and coordinative bonds to give rise to recognition processes. The latter range from molecular recognition in homogeneous phase as well as clathrate formation, to heterogeneous solid-gas and solid-liquid adsorption phenomena. It should be noted that these materials are not rigid but able to undergo guest-induced reorganisation processes even in the solid state. Finally, some of these materials also combine additional interesting magneto-optical properties. Thus, dual systems can be envisaged in which two or more of these properties are present in the same material.

  1. Catabolism of pyrimidines in yeast: A tool to understand degradation of anticancer drugs

    Andersen, Gorm; Merico, A.; Bjornberg, O.; Andersen, Birgit; Schnackerz, K.D.; Dobritzsch, D.; Piskur, Jure; Compagno, C.

    The pyrimidine catabolic pathway is of crucial importance in cancer patients because it is involved in degradation of several chemotherapeutic drugs, such as 5-fluorouracil; it also is important in plants, unicellular eukaryotes, and bacteria for the degradation of pyrimidine-based biocides....../antibiotics. During the last decade we have developed a yeast species, Saccharomyces kluyveri, as a model and tool to study the genes and enzymes of the pyrimidine catabolic pathway. In this report, we studied degradation of uracil and its putative degradation products in 38 yeasts and showed that this pathway was...

  2. ESR study of radiation damage in pyrimidines. Technical progress report, August 1, 1974--July 31, 1975

    The primary objective of this project is to investigate radiation damage to biomolecules using substituted pyrimidines as a model system. Results this year include a general mechanism for iminoxy radical formation in nitropyrimidines, identification of free radical structures in 5-ethyl-5-isopropylbarbituric acid, 5-ethyl-5-isoamylbarbituric acid, and 5-allyl-5-isopropylbarbituric acid, demonstration that the uracilyl radical is formed by hydrogen addition to C(5) of the pyrimidine ring, construction of a k-band microwave cavity for 770K single crystal studies, determination of several dose-response curves, and synthesis of new pyrimidine derivatives for study in the coming year. (U.S.)

  3. Interaction of quinones with three pyrimidine bases: A laser flash photolysis study

    The interaction between three different pyrimidine bases, uracil (U), cytosine (C) and thymine (T) and two quinones, 2-methyl-1,4-naphthoquinone or menadione (MQ) and 9,10-anthraquinone (AQ) have been studied using laser flash photolysis technique in organic homogeneous medium. The three pyrimidines have revealed a difference in their extent of reactivity towards the quinones, which has been attributed to their structural difference. Our works have revealed that the difference in structural dimension of the quinones is also responsible for affecting the reactivity of these pyrimidines in homogeneous medium.

  4. Trisubstituted Pyrimidines as Efficacious and Fast-Acting Antimalarials.

    Norcross, Neil R; Baragaña, Beatriz; Wilson, Caroline; Hallyburton, Irene; Osuna-Cabello, Maria; Norval, Suzanne; Riley, Jennifer; Stojanovski, Laste; Simeons, Frederick R C; Porzelle, Achim; Grimaldi, Raffaella; Wittlin, Sergio; Duffy, Sandra; Avery, Vicky M; Meister, Stephan; Sanz, Laura; Jiménez-Díaz, Belén; Angulo-Barturen, Iñigo; Ferrer, Santiago; Martínez, María Santos; Gamo, Francisco Javier; Frearson, Julie A; Gray, David W; Fairlamb, Alan H; Winzeler, Elizabeth A; Waterson, David; Campbell, Simon F; Willis, Paul; Read, Kevin D; Gilbert, Ian H

    2016-07-14

    In this paper we describe the optimization of a phenotypic hit against Plasmodium falciparum, based on a trisubstituted pyrimidine scaffold. This led to compounds with good pharmacokinetics and oral activity in a P. berghei mouse model of malaria. The most promising compound (13) showed a reduction in parasitemia of 96% when dosed at 30 mg/kg orally once a day for 4 days in the P. berghei mouse model of malaria. It also demonstrated a rapid rate of clearance of the erythrocytic stage of P. falciparum in the SCID mouse model with an ED90 of 11.7 mg/kg when dosed orally. Unfortunately, the compound is a potent inhibitor of cytochrome P450 enzymes, probably due to a 4-pyridyl substituent. Nevertheless, this is a lead molecule with a potentially useful antimalarial profile, which could either be further optimized or be used for target hunting. PMID:27314305

  5. Computational reference data for the photochemistry of cyclobutane pyrimidine dimers.

    Barbatti, Mario

    2014-10-20

    The cis-syn cyclobutane pyrimidine dimer is one of the major classes of carcinogenic UV-induced DNA photoproducts. In this work, diverse high-level quantum-chemical methods were used to determine the spectroscopic properties of neutral (singlet and triplet) and charged (cation and anion) species of thymine dimers. Maps of potential energy, charge distribution, electron affinity, and ionization potential of the thymidine dimers were computed along the two dimerization coordinates for neutral and charged species, as well as for the singlet excited state. This set of data aims at providing consistent results computed with the same methods as for photodamage and repair. Based on these results, several different photo-, heat-, and charge-induced mechanisms of dimerization and repair are characterized and discussed. Additionally, a new stable dimer with methylmethylidene-hexahydropyrimidine structure was found in the S0 state. PMID:25044616

  6. Photorepair of ultraviolet radiation-induced pyrimidine dimers in corneal DNA

    The induction and photrepair of pyrimidine dimers in DNA have been measured in the ultravioletirradiated, corneal epithelium of the marsupial, Monodelphis domestica, using damage-specific nucleases from Micrococcus luteus in conjunction with agarose gel electrophoresis. The authors observed that FS-40 sunlamps induced 7.2 j 1.0 x 10-5 pyrimidine dimers per kilobase (kb) of DNA per J/m2. Following 100 J/m2, 50% and > 90% of the dimers were photorepaired during a 10- and 30-min exposure to photoreactivating light respectively. In addition, 70% and 60% of the dimers induced by 300 and 500 J/m2, respectively, were repaired by a 60-min exposure to photoreactivating light. The capacity of the corneal epithelium of M. domestica to photorepair pyrimidine dimers identifies this animal as a potentially useful model with which to determine whether pyrimidine dimers are involved in pathological changes of the irradiated eye. (author). 29 refs.; 3 figs

  7. The pyrimidine operon pyrRPB-carA from Lactococcus lactis

    Martinussen, Jan; Schallert, J.; Andersen, Birgit;

    2001-01-01

    The four genes pyrR, pyrP, pyrB, and carA were found to constitute an operon in Lactococcus lactis subsp, lactis MG1363. The functions of the different genes were established by mutational analysis. The first gene in the operon is the pyrimidine regulatory gene, pyrR, which is responsible for the...... regulation of the expression of the pyrimidine biosynthetic genes leading to UMP formation. The second gene encodes a membrane-bound high-affinity uracil permease, required for utilization of exogenous uracil. The last two genes in the operon, pyrB and carA, encode pyrimidine biosynthetic enzymes; aspartate...... transcarbamoylase (pyrB) is the second enzyme in the pathway, whereas carbamoyl-phosphate synthetase subunit A (carA) is the small subunit of a heterodimeric enzyme, catalyzing the formation of carbamoyl phosphate. The carA gene product is shown to be required for both pyrimidine and arginine biosynthesis. The...

  8. The relationship between pyrimidine dimers and replicating DNA in UV-irradiated human fibroblasts

    The relationship between pyrimidine dimers (measured as endonuclease-sensitive sites) and newly-synthesized DNA was examined in UV-irradiated normal and XP variant human fibroblasts. Following irradiation of normal cells, the frequency of pyrimidine dimer sites in sections of DNA which had been synthesized immediately before the UV-irradiation was similar to that in the bulk DNA. The frequency of pyrimidine dimer sites in the parental strands of replicating DNA in irradiated normal cells was similar to that in the bulk DNA. In UV-irradiated XP variant cells, the size of DNA synthesized in the presence of caffeine immediately after irradiation accurately corresponded with the average interdimer distance in the parental DNA. This suggested that in this experimental situation each pyrimidine dimer gives rise to a discontinuity or a termination site in the daughter strand. (author)

  9. Synthesis of 2-Arylimidazo[1,2-a]pyrimidines in Ionic Liquids

    Dan Qian XU; Bao You LIU; Zhen Yuan XU

    2003-01-01

    Room temperature ionic liquids were used as a "green" recyclable alternative toconventional solvents in the synthesis of pharmaceutically useful compounds 2-arylimidazo[1, 2-a]pyrimidines through Tschotschibabin reaction of α-bromoacetophenones with 2-aminopyfinidinein good yields.

  10. A convenient route for synthesis and antimicrobial evaluation of bis (diimino benzothiazolo pyrimido pyrimidines

    Balasaheb D. Kalyankar

    2014-12-01

    Full Text Available Guanidine hydrochloride (1 on treatment with bis(methylthiomethylene malonitrile (2 in N,N-dimethyl formamide (DMF and catalytic amount of anhydrous potassium carbonate gives diimino pyrimido pyrimidine (3. The later were further reacted with various substituted 2-amino benzothiazoles (4 to gives bis (diimino benzothiazolo pyrimido pyrimidines (5a-g. All these synthesized compounds were screened for their antimicrobial activity.

  11. Metabolism of pyrimidine bases and nucleosides in the coryneform bacteria Brevibacterium ammoniagenes and Micrococcus luteus.

    Auling, G; Moss, B

    1984-01-01

    The metabolism of exogenous pyrimidine bases and nucleosides was investigated in Brevibacterium ammoniagenes and Micrococcus luteus with fluorinated analogs and radioactive precursors. Salvage of thymine and thymidine was found in M. luteus, but not in B. ammoniagenes. Exogenous uracil or uracil nucleosides, but not cytosine or cytosine nucleosides, were nucleic acid precursors for both bacteria. By examining the possible nucleoside-metabolizing enzymes, it can be suggested that the pyrimidin...

  12. Investigation of UVC Induced DNA Damage Formation and Photolyase Catalyzed Repair of Cyclobutane Pyrimidine Dimers

    Kundu, Lal Mohan

    2005-01-01

    Gradual depletion of the ozone layer and consequently, increased ultraviolet (UV) radiation on the Earth's surface induces DNA-lesions inside the genome, thereby causing mutations. Three kinds of photoproducts are mainly formed, namely: cyclobutane pyrimidine dimers (CPD), pyrimidine-(6-4)-pyrimidone dimer [(6-4)PP] and the Dewar valence isomer of (6-4)PP lesion. The formation of these photolesions is a major cause of cell death (aging) and fatal disease like skin cancer. ...

  13. The pyrimidine nucleotide carrier PNC1 and mitochondrial trafficking of thymidine phosphates in cultured human cells

    Franzolin, Elisa; Miazzi, Cristina; Frangini, Miriam; Palumbo, Elisa; Rampazzo, Chiara [Department of Biology, University of Padova, Via Ugo Bassi 58B, I-35131 Padova (Italy); Bianchi, Vera, E-mail: vbianchi@bio.unipd.it [Department of Biology, University of Padova, Via Ugo Bassi 58B, I-35131 Padova (Italy)

    2012-10-15

    In cycling cells cytosolic de novo synthesis of deoxynucleotides is the main source of precursors for mitochondrial (mt) DNA synthesis. The transfer of deoxynucleotides across the inner mt membrane requires protein carriers. PNC1, a SLC25 family member, exchanges pyrimidine nucleoside triphosphates in liposomes and its downregulation decreases mtUTP concentration in cultured cells. By an isotope-flow protocol we confirmed transport of uridine nucleotides by PNC1 in intact cultured cells and investigated PNC1 involvement in the mt trafficking of thymidine phosphates. Key features of our approach were the manipulation of PNC1 expression by RNA interference or inducible overexpression, the employment of cells proficient or deficient for cytosolic thymidine kinase (TK1) to distinguish the direction of flow of thymidine nucleotides across the mt membrane during short pulses with [{sup 3}H]-thymidine, the determination of mtdTTP specific radioactivity to quantitate the rate of mtdTTP export to the cytoplasm. Downregulation of PNC1 in TK1{sup -} cells increased labeled dTTP in mitochondria due to a reduced rate of export. Overexpression of PNC1 in TK1{sup +} cells increased mtdTTP pool size and radioactivity, suggesting an involvement in the import of thymidine phosphates. Thus PNC1 is a component of the network regulating the mtdTTP pool in human cells. -- Highlights: Black-Right-Pointing-Pointer Thymidine phosphates exchange between mitochondria and cytosol in mammalian cells. Black-Right-Pointing-Pointer siRNA-downregulation of PNC1 delays mitochondrial dTTP export in TK1{sup -} cells. Black-Right-Pointing-Pointer PNC1 overexpression accumulates dTTP in mitochondria of TK1{sup +} cells. Black-Right-Pointing-Pointer PNC1 exchanges thymidine nucleotides across the mitochondrial inner membrane. Black-Right-Pointing-Pointer PNC1 participates in the regulation of the mtdTTP pool supporting mtDNA synthesis.

  14. The pyrimidine nucleotide carrier PNC1 and mitochondrial trafficking of thymidine phosphates in cultured human cells

    In cycling cells cytosolic de novo synthesis of deoxynucleotides is the main source of precursors for mitochondrial (mt) DNA synthesis. The transfer of deoxynucleotides across the inner mt membrane requires protein carriers. PNC1, a SLC25 family member, exchanges pyrimidine nucleoside triphosphates in liposomes and its downregulation decreases mtUTP concentration in cultured cells. By an isotope-flow protocol we confirmed transport of uridine nucleotides by PNC1 in intact cultured cells and investigated PNC1 involvement in the mt trafficking of thymidine phosphates. Key features of our approach were the manipulation of PNC1 expression by RNA interference or inducible overexpression, the employment of cells proficient or deficient for cytosolic thymidine kinase (TK1) to distinguish the direction of flow of thymidine nucleotides across the mt membrane during short pulses with [3H]-thymidine, the determination of mtdTTP specific radioactivity to quantitate the rate of mtdTTP export to the cytoplasm. Downregulation of PNC1 in TK1− cells increased labeled dTTP in mitochondria due to a reduced rate of export. Overexpression of PNC1 in TK1+ cells increased mtdTTP pool size and radioactivity, suggesting an involvement in the import of thymidine phosphates. Thus PNC1 is a component of the network regulating the mtdTTP pool in human cells. -- Highlights: ► Thymidine phosphates exchange between mitochondria and cytosol in mammalian cells. siRNA-downregulation of PNC1 delays mitochondrial dTTP export in TK1− cells. ► PNC1 overexpression accumulates dTTP in mitochondria of TK1+ cells. ► PNC1 exchanges thymidine nucleotides across the mitochondrial inner membrane. ► PNC1 participates in the regulation of the mtdTTP pool supporting mtDNA synthesis.

  15. Selective inhibition by methoxyamine of the apurinic/apyrimidinic endonuclease activity associated with pyrimidine dimer-DNA glycosylases from Micrococcus luteus and bacteriophage T4

    The UV endonucleases from Micrococcus luteus and bacteriophage T4 possess two catalytic activities specific for the site of cyclobutane pyrimidine dimers in UV-irradiated DNA: a DNA glycosylase that cleaves the 5'-glycosyl bond of the dimerized pyrimidines and an apurinic/apyrimidinic (AP) endonuclease that thereupon incises the phosphodiester bond 3' to the resulting apyrimidinic site. The authors have explored the potential use of methoxyamine, a chemical that reacts at neutral pH with AP sites in DNA, as a selective inhibitor of the AP endonuclease activities residing in the M. luteus and T4 enzymes. The presence of 50 mM methoxyamine during incubation of UV-treated, [3H]thymine-labeled poly(dA) x poly(dT) with either enzyme preparation was found to protect completely the irradiated copolymer from endonucleolytic attack at dimer sites, as assayed by yield of acid-soluble radioactivity. In contrast, the dimer-DNA glycosylase activity of each enzyme remained fully functional, as monitored retrospectively by release of free thymine after either photochemical-(5 kJ/m2, 254 nm) or photoenzymic- (Escherichia coli photolyase plus visible light) induced reversal of pyrimidine dimers in the UV-damaged substrate. The data demonstrate that the inhibition of the strand-incision reaction arises because of chemical modification of the AP sites and is not due to inactivation of the enzyme by methoxyamine. The results, combined with earlier findings for 5'-acting AP endonucleases, strongly suggest that methoxyamine is a highly specific inhibitor of virtually all AP endonucleases, irrespective of their modes of action, and may therefore prove useful in a wide variety of DNA repair studies

  16. catena-Poly[bis­[cis-dipyrimidine-trans-dithio­cyanato­iron(II)]-di-μ-pyrimidine-[trans-dithio­cyanato­iron(II)]-di-μ-pyrimidine

    Wriedt, Mario; Sellmer, Sina; Jess, Inke; Näther, Christian

    2009-01-01

    In the crystal structure of the title compound, [Fe3(NCS)6(C4H4N2)8] n , each iron(II) cation is coordinated by four N-bonded pyrimidine ligands and two N-bonded thio­cyanate anions in a distorted octa­hedral environment. The asymmetric unit consists of one iron cation located on a crystallographic center of inversion, as well as one iron cation, three thio­cyanate anions and four pyrimidine ligands occupying general positions. The structure consists of square secondary building units (SBUs) ...

  17. Food labels

    Selsøe Sørensen, Henrik; Clement, Jesper; Gabrielsen, Gorm

    2012-01-01

    The food industry develops tasty and healthy food but fails to deliver the message to all consumers. The consumers’ background knowledge is essential for how they find and decode relevant elements in the cocktail of signs which fight for attention on food labels. In this exploratory study, we find...... evidence for dividing consumers into two profiles: one relying on general food knowledge and another using knowledge related to signpost labels. In a combined eyetracking and questionnaire survey we analyse the influence of background knowledge and identify different patterns of visual attention for the...... two consumer profiles. This underlines the complexity in choosing and designing the ‘right’ elements for a food package that consumers actually look at and are able to make rational use of. In spite of any regulation of food information provided by authorities, consumers will still be confronted with...

  18. Environmental Labeling

    Andrea Podhorsky

    2009-01-01

    This paper studies how information disclosed by voluntary environmental labels creates incentives for firms to invest in environmentally-friendly production technologies. I develop a model with differentiated products and imperfectly-informed consumers. Consumers care about the environmental characteristics of goods (for example, how they were produced), but cannot directly observe these product characteristics. Firms differ in their abilities to develop "clean" technologies, but have no ince...

  19. Quantitation of radiation-, chemical-, or enzyme-induced single strand breaks in nonradioactive DNA by alkaline gel electrophoresis: application to pyrimidine dimers

    The authors have developed an alkaline agarose gel method for quantitating single strand breaks in nanogram quantities of nonradioactive DNA. After electrophoresis together with molecular length standards, the DNA is neutralized, stained with ethidium bromide, photographed, and the density profiles recorded with a computer controller scanner. The medium lengths, number average molecular lengths, and length average molecular lengths of the DNAs can be computed by using the mobilities of the molecular length standards. The frequency of single strand breaks can then be determined by comparison of the corresponding average molecular lengths of DNAs treated and not treated with single stand break-inducing agents (radiation, chemicals, or lesion-specific endonuclease). Single stand break yields (induced at pyrimidine dimer sites in uv-irradiated human fibroblasts DNA by the dimer-specific endonuclease from Micrococcus luteus) from our method agree with values obtained for the same DNAs from alkaline sucrose gradient analysis. The method has been used to determined pyrimidine dimer yields in DNA from biopsies of human skin irradiated in situ. It will be especially useful in determining the frequency of single strand breaks (or lesions convertible to single stand breaks by specific cleaving reagents or enzymes) in small quantities of DNA from cells or tissues not amendable to radioactive labeling

  20. Synthesis and NMR of {sup 15}N-labeled DNA fragments

    Jones, R.A. [Rutgers, The State Univ. of New Jersey, Piscataway, NJ (United States)

    1994-12-01

    DNA fragments labeled with {sup 15}N at the ring nitrogens and at the exocyclic amino groups can be used to obtain novel insight into interactions such as base pairing, hydration, drug binding, and protein binding. A number of synthetic routes to {sup 15}N-labeled pyrimidine nucleosides, purines, and purine nucleosides have been reported. Moreover, many of these labeled bases or monomers have been incorporated into nucleic acids, either by chemical synthesis or by biosynthetic procedures. The focus of this chapter will be on the preparation of {sup 15}N-labeled purine 2{prime}-deoxynucleosides, their incorporation into DNA fragments by chemical synthesis, and the results of NMR studies using these labeled DNA fragments.

  1. De novo pyrimidine biosynthesis in the oomycete plant pathogen Phytophthora infestans.

    García-Bayona, Leonor; Garavito, Manuel F; Lozano, Gabriel L; Vasquez, Juan J; Myers, Kevin; Fry, William E; Bernal, Adriana; Zimmermann, Barbara H; Restrepo, Silvia

    2014-03-10

    The oomycete Phytophthora infestans, causal agent of the tomato and potato late blight, generates important economic and environmental losses worldwide. As current control strategies are becoming less effective, there is a need for studies on oomycete metabolism to help identify promising and more effective targets for chemical control. The pyrimidine pathways are attractive metabolic targets to combat tumors, virus and parasitic diseases but have not yet been studied in Phytophthora. Pyrimidines are involved in several critical cellular processes and play structural, metabolic and regulatory functions. Here, we used genomic and transcriptomic information to survey the pyrimidine metabolism during the P. infestans life cycle. After assessing the putative gene machinery for pyrimidine salvage and de novo synthesis, we inferred genealogies for each enzymatic domain in the latter pathway, which displayed a mosaic origin. The last two enzymes of the pathway, orotate phosphoribosyltransferase and orotidine-5-monophosphate decarboxylase, are fused in a multi-domain enzyme and are duplicated in some P. infestans strains. Two splice variants of the third gene (dihydroorotase) were identified, one of them encoding a premature stop codon generating a non-functional truncated protein. Relative expression profiles of pyrimidine biosynthesis genes were evaluated by qRT-PCR during infection in Solanum phureja. The third and fifth genes involved in this pathway showed high up-regulation during biotrophic stages and down-regulation during necrotrophy, whereas the uracil phosphoribosyl transferase gene involved in pyrimidine salvage showed the inverse behavior. These findings suggest the importance of de novo pyrimidine biosynthesis during the fast replicative early infection stages and highlight the dynamics of the metabolism associated with the hemibiotrophic life style of pathogen. PMID:24361203

  2. Photochemistry of Pyrimidine in Astrophysical Ices: Formation of Nucleobases and Other Prebiotic Species

    Nuevo, Michel; Sandford, Scott A.; Materese, Christopher K.; Milam, Stefanie N.

    2012-01-01

    Nucleobases are N-heterocycles that are the informational subunits of DNA and RNA. They are divided into two molecular groups: pyrimidine bases (uracil, cytosine, and thymine) and purine bases (adenine and guanine). Nucleobases have been detected in meteorites, and their extraterrestrial origin confirmed by isotopic measurements. Although no N-heterocycles have ever been observed in the ISM, the positions of the 6.2- m interstellar emission features suggest a population of such molecules is likely to be present. However, laboratory experiments have shown that the ultraviolet (UV) irradiation of pyrimidine in ices of astrophysical relevance such as H2O, NH3, CH3OH, CH4, CO, or combinations of these at low temperature (less than or equal to 20 K) leads to the formation of several pyrimidine derivatives including the nucleobases uracil and cytosine, as well as precursors such as 4(3H)-pyrimidone and 4-aminopyrimidine. Quantum calculations on the formation of 4(3H)-pyrimidone and uracil from the irradiation of pyrimidine in pure H2O ices are in agreement with their experimental formation pathways.10 In those residues, other species of prebiotic interest such as urea as well as the amino acids glycine and alanine could also be identified. However, only very small amounts of pyrimidine derivatives containing CH3 groups could be detected, suggesting that the addition of methyl groups to pyrimidine is not an efficient process. For this reason, the nucleobase thymine was not observed in any of the samples. In this work, we study the formation of nucleobases and other photo-products of prebiotic interest from the UV irradiation of pyrimidine in ices containing H2O, NH3, CH3OH, and CO, mixed in astrophysical proportions.

  3. Potential formation of three pyrimidine bases in interstellar regions

    Majumdar, Liton; Das, Ankan; Chakrabarti, Sandip K

    2015-01-01

    Work on the chemical evolution of pre-biotic molecules remains incomplete since the major obstacle is the lack of adequate knowledge of rate coefficients of various reactions which take place in interstellar conditions. In this work, we study the possibility of forming three pyrimidine bases, namely, cytosine, uracil and thymine in interstellar regions. Our study reveals that the synthesis of uracil from cytosine and water is quite impossible under interstellar circumstances. For the synthesis of thymine, reaction between uracil and :CH2 is investigated. Since no other relevant pathways for the formation of uracil and thymine were available in the literature, we consider a large gas-grain chemical network to study the chemical evolution of cytosine in gas and ice phases. Our modeling result shows that cytosine would be produced in cold, dense interstellar conditions. However, presence of cytosine is yet to be established. We propose that a new molecule, namely, C4N3OH5 could be observable in the interstellar ...

  4. De novo pyrimidine biosynthesis is required for virulence of Toxoplasma gondii.

    Fox, Barbara A; Bzik, David J

    2002-02-21

    Toxoplasma gondii is a ubiquitous protozoan parasite that is responsible for severe congenital birth defects and fatal toxoplasmic encephalitis in immunocompromized people. Fundamental aspects of obligate intracellular replication and pathogenesis are only now beginning to emerge for protozoan parasites. T. gondii has a fragmented pathway for salvaging pyrimidine nucleobases derived from the parasite or host cell, and this limited pyrimidine salvage capacity is funnelled exclusively through uracil phosphoribosyltransferase. Disrupting the function of this enzyme does not affect the growth of T. gondii tachyzoites, which suggests that the de novo pyrimidine biosynthesis pathway may be necessary for growth. We have examined the virulence of T. gondii mutants that lack carbamoyl phosphate synthetase II (uracil auxotrophs) to determine whether de novo pyrimidine biosynthesis is required in vivo. Here we show that T. gondii uracil auxotrophs are completely avirulent not only in immune-competent BALB/c mice but also in mice that lack interferon-gamma. A single injection of the uracil auxotroph into BALB/c mice induces long-term protective immunity to toxoplasmosis. Our findings indicate the significance of the de novo pyrimidine biosynthesis pathway for the virulence of parasitic protozoa, and suggest routes for developing vaccines and chemotherapy. PMID:11859373

  5. DNA repair after ultraviolet irradiation of ICR 2A frog cells: pyrimidine dimers are long acting blocks to nascent DNA synthesis

    The ability of ICR 2A frog cells to repair DNA damage induced by ultraviolet irradiation was examined. These cells are capable of photoreactivation but are nearly totally deficient in excision repair. They have the ability to convert the small molecular weight DNA made after irradiation into large molecules but do not show an enhancement in this process when the UV dose is delivered in two separate exposures separated by a 3- or 24-h incubation. Total DNA synthesis is depressed and low molecular weight DNA continues to be synthesized during pulse-labeling as long as 48 h after irradiation. The effects of pyrimidine dimer removal through exposure of UV irradiated cells to photoreactivating light indicate that dimers act as the critical lesions blocking DNA synthesis

  6. Synthesis and Antimicrobial Studies of Pyrimidine Pyrazole Heterocycles

    Rakesh Kumar

    2014-01-01

    Full Text Available Prompted from the diversity of the wider use and being an integral part of genetic material, an effort was made to synthesize pyrimidine pyrazole derivatives of pharmaceutical interest by oxidative cyclization of chalcones with satisfactory yield and purity. A novel series of 1,3-dimethyl-6-hydroxy-2,4-dioxo-5-(1′-phenyl-3′-aryl-1H-pyrazol-5′-yl-1,2,3,4-tetrahydropyrimidines (5a–d and 1,3-diaryl-6-hydroxy-4-oxo-2-thioxo-5-(1′-phenyl-3′-aryl-1H-pyrazol-5′-yl-1,2,3,4-tetrahydropyrimidines (5e–l has been synthesized. The structures of these compounds were established on the basis of FT-IR, 1H NMR, 13C NMR, and mass spectral analysis. All the synthesized compounds were screened for their antimicrobial activity against bacteria and fungi. Among all the compounds, 5g was found to be the most active as its MIC was 31.25 µg/mL against S. aureus and B. cereus. The compounds 5h, 5c, and 5e also possess antibacterial activity with MIC values as 62.50, 125.00, and 500.00 µg/mL, respectively. The compounds 5c and 5j were found to have antifungal activity against Aspergillus spp. As antifungal drugs lag behind the antibacterial drugs, therefore we tried in vitro combination of these two compounds with standard antifungal drugs (polyene and azole against Aspergillus spp. The combination of ketoconazole with 5c and 5j showed synergy at 1 : 8 (6.25 : 50.00 µg/mL and 1 : 4 (25 : 100 µg/mL against A. fumigatus (ITCC 4517 and A. fumigatus (VPCI 190/96, respectively.

  7. Photoreactivation of UV-induced pyrimidine dimers and erythema in the marsupial Monodelphis domestica

    Post-UV treatment of the gray, short-tailed opossum Monodelphis domestica with photoreactivating light (320-400 nm) suppressed the appearance of UV-induced erythema as evidenced by an increase in the dose of UV required to elicit an erythemal response. Pre-UV exposure to photoreactivating light had no effect on the UV induction of erythema. The dose-response for the photoreversal of pyrimidine dimers in epidermal DNA of M. domestica was similar to that for the photoreactivation of erythema induction. These data not only support the notion that DNA is the primary chromophore involved in the induction of erythema but also identify pyrimidine dimers as the major DNA change responsible for its induction. These results also identify M. domestica as a useful whole-animal system with which to determine the role of pyrimidine dimers in other photobiological responses of mammalian skin

  8. Photoreactivation of UV-induced pyrimidine dimers and erythema in the marsupial Monodelphis domestica

    Ley, R.D.

    1985-04-01

    Post-UV treatment of the gray, short-tailed opossum Monodelphis domestica with photoreactivating light (320-400 nm) suppressed the appearance of UV-induced erythema as evidenced by an increase in the dose of UV required to elicit an erythemal response. Pre-UV exposure to photoreactivating light had no effect on the UV induction of erythema. The dose-response for the photoreversal of pyrimidine dimers in epidermal DNA of M. domestica was similar to that for the photoreactivation of erythema induction. These data not only support the notion that DNA is the primary chromophore involved in the induction of erythema but also identify pyrimidine dimers as the major DNA change responsible for its induction. These results also identify M. domestica as a useful whole-animal system with which to determine the role of pyrimidine dimers in other photobiological responses of mammalian skin.

  9. Nucleobases and Other Prebiotic Species from the UV Irradiation of Pyrimidine in Astrophysical Ices

    Sandford, Scott; Materese, Christopher; Nuevo, Michel

    2012-01-01

    Nucleobases are aromatic N-heterocycles that constitute the informational subunits of DNA and RNA and are divided into two families: pyrimidine bases (uracil, cytosine, and thymine) and purine bases (adenine and guanine). Nucleobases have been detected in meteorites and their extraterrestrial origin confirmed by isotope measurement. Although no N-heterocycles have been individually identified in the ISM, the 6.2-micron interstellar emission feature seen towards many astronomical objects suggests a population of such molecules is likely present. We report on a study of the formation of pyrimidine-based molecules, including nucleobases and other species of prebiotic interest, from the ultraviolet (UV) irradiation of pyrimidine in low temperature ices containing H2O, NH3, C3OH, and CH4, to simulate the astrophysical conditions under which prebiotic species may be formed in the Solar System.

  10. Erwinia amylovora pyrC mutant causes fire blight despite pyrimidine auxotrophy.

    Ramos, L S; Sinn, J P; Lehman, B L; Pfeufer, E E; Peter, K A; McNellis, T W

    2015-06-01

    Erwinia amylovora bacteria cause fire blight disease, which affects apple and pear production worldwide. The Erw. amylovora pyrC gene encodes a predicted dihydroorotase enzyme involved in pyrimidine biosynthesis. Here, we discovered that the Erw. amylovora pyrC244::Tn5 mutant was a uracil auxotroph. Unexpectedly, the Erw. amylovora pyrC244::Tn5 mutant grew as well as the wild-type in detached immature apple and pear fruits. Fire blight symptoms caused by the pyrC244::Tn5 mutant in immature apple and pear fruits were attenuated compared to those caused by the wild-type. The pyrC244::Tn5 mutant also caused severe fire blight symptoms in apple tree shoots. A plasmid-borne copy of the wild-type pyrC gene restored prototrophy and symptom induction in apple and pear fruit to the pyrC244::Tn5 mutant. These results suggest that Erw. amylovora can obtain sufficient pyrimidine from the host to support bacterial growth and fire blight disease development, although de novo pyrimidine synthesis by Erw. amylovora is required for full symptom development in fruits. Significance and impact of the study: This study provides information about the fire blight host-pathogen interaction. Although the Erwinia amylovora pyrC mutant was strictly auxotrophic for pyrimidine, it grew as well as the wild-type in immature pear and apple fruits and caused severe fire blight disease in apple trees. This suggests that Erw. amylovora can obtain sufficient pyrimidines from host tissue to support growth and fire blight disease development. This situation contrasts with findings in some human bacterial pathogens, which require de novo pyrimidine synthesis for growth in host blood, for example. PMID:25789570

  11. Biochemical and molecular characterization of the pyrimidine biosynthetic enzyme dihydroorotate dehydrogenase from Toxoplasma gondii

    Triana, Miryam Andrea Hortua; Huynh, My-Hang; Manuel F Garavito; Fox, Barbara A.; Bzik, David J.; Vern B Carruthers; Löffler, Monika; Zimmermann, Barbara H.

    2012-01-01

    The pyrimidine biosynthesis pathway in the protozoan pathogen Toxoplasma gondii is essential for parasite growth during infection. To investigate the properties of dihydroorotate dehydrogenase (TgDHOD), the fourth enzyme in the T. gondii pyrimidine pathway, we expressed and purified recombinant TgDHOD. TgDHOD exhibited a specific activity of 84 U/mg, a kcat of 89 sec−1, a Km = 60 μM for L-dihydroorotate, and a Km = 29 μM for decylubiquinone (QD). Quinones lacking or having short isoprenoid si...

  12. Design, synthesis and cytotoxic activity of some novel compounds containing pyrazolo[3,4-]pyrimidines nucleus

    Manal M Kandeel; Sameha M Roshdy; Eman K A Abdelall; Mohamed A Abdelgawad; Phoebe F Lamie

    2013-09-01

    Novel pyrazolo[3,4-]pyrimidines were designed and synthesized as antitumour agents against human breast cancer adenoma (MCF-7). Molecular modelling and pharmacological screening were performed against breast cancer cell line and also certain synthetic pathways were developed in order to introduce functionality onto C6 and N5 positions of pyrimidine moiety. Surprisingly, all the test compounds showed IC50 lower than that of the standard olomoucine I, especially compounds 4b, 8a, 10b, 11a and b, which showed IC50 between 0.009 and 0.004 M.

  13. Studies on Synthesis of Some New Chalcone and Pyrimidines and their Antibacterial Activity

    Ketan Mistry; K. R. Desai

    2005-01-01

    Pyrimidine-2-one derivatives, 2-[2-{1ʹ-(p-nitrophenyl)-6ʹ-(substituted-phenyl)-pyrimidine-2ʹ-one-4ʹ-yl}-hydrazinomethyl]-3-(p-methoxy phenyl)-quina-zoline-4(3H)-one [4a-j] have been synthesised by the condensation of p-nitro phenylurea and various chalcones, 2-(substituted phenylchalconylhydrazinomethyl)-3-(p-methoxyphenyl)-quinazoline-4(3H)-one [3a-j] in the presence of catalytic amount of conc. HCl. And this series of chalcones have been synthesised by the reaction of 2-acetylhydrazinomethy...

  14. Nucleobases and other Prebiotic Species from the Ultraviolet Irradiation of Pyrimidine in Astrophysical Ices

    Sandford, S. A.; Nuevo, M.; Materese, C. K.; Milam, S. N.

    2012-01-01

    Nucleobases are N-heterocycles that are the informational subunits of DNA and RNA, and are divided into two families: pyrimidine bases (uracil, cytosine, and thymine) and purine bases (adenine and guanine). Nucleobases have been detected in meteorites and their extraterrestrial origin confirmed by isotope measurement. Although no Nheterocycles have ever been observed in the ISM, the positions of the 6.2-m interstellar emission features suggest a population of such molecules is likely to be present. In this work we study the formation of pyrimidine-based molecules, including nucleobases, as well as other species of prebiotic interest, from the ultraviolet (UV) irradiation of pyrimidine in combinations of H2O, NH3, CH3OH, and CH4 ices at low temperature, in order to simulate the astrophysical conditions under which prebiotic species may be formed in the interstellar medium and icy bodies of the Solar System. Experimental: Gas mixtures are prepared in a glass mixing line (background pressure approx. 10(exp -6)-10(exp -5) mbar). Relative proportions between mixture components are determined by their partial pressures. Gas mixtures are then deposited on an aluminum foil attached to a cold finger (15-20 K) and simultaneously irradiated with an H2 lamp emitting UV photons (Lyman and a continuum at approx.160 nm). After irradiation samples are warmed to room temperature, at which time the remaining residues are recovered to be analyzed with liquid and gas chromatographies. Results: These experiments showed that the UV irradiation of pyrimidine mixed in these ices at low temperature leads to the formation of several photoproducts derived from pyrimidine, including the nucleobases uracil and cytosine, as well as their precursors 4(3H)-pyrimidone and 4-aminopyrimidine (Fig. 1). Theoretical quantum calculations on the formation of 4(3H)-pyrimidone and uracil from the irradiation of pyrimidine in pure H2O ices are in agreement with their experimental formation pathways. In

  15. Synthesis and biological evaluation of new pyrazolo[3,4-d]pyrimidine derivatives

    Asma Agrebi; Fatma Allouche; Hamadi Fetoui; Fakher Chabchoub

    2014-01-01

    Several new pyrazolopyrimidine compounds were achieved from aminocyanopyarazole 1. The starting material 1 was initially coupled with orthoester at refluxed with various primary amines, ammonia, hydrazines and hydroxylamine to furnish a series of pyrazolo[3,4-d]pyrimidines. The reaction of imidate 2a-b with hydrazide derivatives led to the formation of pyrazolo[3,4-d][1,2,4]triazolo[4,3-c]pyrimidines. Some of the synthesized compounds 3a and 4c were evaluated for the...

  16. New one-pot synthesis of spiro[furo[2,3-d]pyrimidine-6,5'-pyrimidine]pentaones and their sulfur analogues.

    Jalilzadeh, Mohammad; Noroozi Pesyan, Nader; Rezaee, Fereshteh; Rastgar, Saeed; Hosseini, Yaser; Sahin, Ertan

    2011-08-01

    Reaction of barbituric acid (BA), 1,3-dimethyl barbituric acid (DMBA) and 2-thiobarbituric acid (TBA) with cyanogen bromide and various aldehydes in presence of triethylamine afforded a new class of heterocyclic stable 5-alkyl and/or 5-aryl-1H, 1'H-spiro[furo[2,3-d]pyrimidine-6,5'-pyrimidine]2,2',4,4',6'(3H,3'H,5H)-pentaones which are dimeric forms of barbiturate (uracil and thiouracil derivatives) at 0 °C to ambient temperatures. Structure elucidation is proved by X-ray crystallography, (1)H NMR, (13)C NMR, FT-IR, CHN and mass analyses techniques. Mechanisms of the formations are discussed. PMID:21279439

  17. Synthesis and anti-inflammatory activity of imidazo [1,2-a] pyrimidine derivatives

    Jin Pei Zhou; Yi Wei Ding; Hui Bin Zhang; Lian Xu; Yue Dai

    2008-01-01

    A series of imidazo [1,2-a] pyrimidine derivatives substituted adjacently with two aryls at positions 2 and 3 were designed and synthesized in order to improve their anti-inflammatory activities. Biological tests suggested that these compounds have antiinflammatory activities with COX-2 selectivity to some extent.

  18. Pyrimidine acyclic nucleoside phosphonates and their phosphorylated analogs as potential multisubstrate inhibitors of thymidine phosphorylase

    Pomeisl, Karel; Votruba, Ivan; Holý, Antonín; Pohl, Radek; Blažek, Jiří; Krečmerová, Marcela

    Ottawa : -, 2012. -. [Ottawa 2012 International Symposium On Biochemistry and Biophysics. 24.10.2012-25.10.2012, Ottawa] R&D Projects: GA MPO FR-TI4/625 Institutional support: RVO:61388963 Keywords : acyclic nucleoside phosphonates * thymidine phosphorylase * phosphorylation * pyrimidines Subject RIV: CC - Organic Chemistry

  19. Excision repair of UVR-induced pyrimidine dimers in corneal DNR

    We measured excision repair of ultraviolet radiation (UVR)-induced pyrimidine dimers in DNA of the corneal epithelium of the marsupial, Monodelphis domestica, using damage-specific nucleases from Micrococcus luteus in conjunction with agarose gel electrophoresis. We observed that 100 J m-2 of UVR from a FS-40 sunlamp (280-400 nm) induced an average of 2.2 +- 0.2x 10-2 endonuclease-sensitive sites per kilobase (ESS/kb) (pyrimidine dimers) and that ∼ 50% of the dimers were repaired within 12 h after exposure. We also determined that an exposure of 400 J m-2 was needed to induce comparable numbers of pyrimidine dimers (2.5 x 10-2) in the DNA of skin of M. domestica in vivo. In addition, we found that 50% of the dimers were also removed from the epidermal cells of M. domestica within 12 h after exposure. A dose of 100 J m-2 was necessary to induce similar levels of pyrimidine dimers (2.0 +- 0.2 x 10-2) in the DNA of the cultured marsupial cell line Pt K2 (Potorous tridactylus). (author)

  20. Excision repair of UVR-induced pyrimidine dimers in corneal DNR

    Freeman, S.E.; Applegate, L.A.; Ley, R.D.

    1988-01-01

    We measured excision repair of ultraviolet radiation (UVR)-induced pyrimidine dimers in DNA of the corneal epithelium of the marsupial, Monodelphis domestica, using damage-specific nucleases from Micrococcus luteus in conjunction with agarose gel electrophoresis. We observed that 100 J m/sup -2/ of UVR from a FS-40 sunlamp (280-400 nm) induced an average of 2.2 +- 0.2x 10/sup -2/ endonuclease-sensitive sites per kilobase (ESS/kb) (pyrimidine dimers) and that approx. 50% of the dimers were repaired within 12 h after exposure. We also determined that an exposure of 400 J m/sup -2/ was needed to induce comparable numbers of pyrimidine dimers (2.5 x 10/sup -2/) in the DNA of skin of M. domestica in vivo. In addition, we found that 50% of the dimers were also removed from the epidermal cells of M. domestica within 12 h after exposure. A dose of 100 J m/sup -2/ was necessary to induce similar levels of pyrimidine dimers (2.0 +- 0.2 x 10/sup -2/) in the DNA of the cultured marsupial cell line Pt K2 (Potorous tridactylus).

  1. Synthesis of novel isoxazolyl bis-thiazolo[3,2-a]pyrimidines

    E. Rajanarendar; S. Ramakrishna; K. Rama Murthy

    2012-01-01

    A new synthetic strategy for the synthesis of novel 3-(3-(3-methyl-4-nitroisoxazol-5-yl)-2-phenyl-1-(5,7-diaryl-7H-thiazolo[3,2-a]pyrimidin-3-yl)propyl)-5,7-diaryl-7H-thiazolo[3,2-a]pyrimidines (7a-i) analogues is described.Reaction of 3-(2-(3-methyl-4-nitroisoxazole-5-yl)-1-phenylethyl)pentane-2,4-dione (3) with two moles of thiourea in presence of iodine and CuO afforded 4-(1-(2-aminothiazol-4-yl)-3-(3-methyl-4-nitroisoxazol-5-yl)-2-aryl propylthiazol-2-amine (5).Compound 5 on reaction with two moles of chalcone (6) furnished novel 3-(3-(3-methyl-4-nitroisoxazol-5-yl)-2-phenyl-l-(5,7-diaryl-7H-thiazolo[3,2-a]pyrimidin-3-yl)propyl)-5,7-diaryl-7H-thiazolo[3,2-a]pyrimidines (7a-i).

  2. An Efficient and Facile Methodology for Bromination of Pyrimidine and Purine Nucleosides with Sodium Monobromoisocyanurate (SMBI

    Roger Stromberg

    2013-10-01

    Full Text Available An efficient and facile strategy has been developed for bromination of nucleosides using sodium monobromoisocyanurate (SMBI. Our methodology demonstrates bromination at the C-5 position of pyrimidine nucleosides and the C-8 position of purine nucleosides. Unprotected and also several protected nucleosides were brominated in moderate to high yields following this procedure.

  3. Tumour radiosensitization with the halogenated pyrimidines 5'-bromo-and 5'-iododeoxyuridine

    Epstein, A.H.; Cook, J.A.; Goffman, T. (National Cancer Inst., Bethesda, MD (United States)); Glatstein, E. (Texas Univ., Dallas, TX (United States). Southwestern Medical Center)

    1993-02-01

    The authors review studies of the use of iododeoxyuridine (IdUrd) and bromodeoxyuridine as radiosensitizers and attempt to correlate the clinical outcome for patients treated with radiation and IdUrd with the extent of halogenated pyrimidine cellular uptake and incorporation. (U.K.).

  4. Tumour radiosensitization with the halogenated pyrimidines 5'-bromo-and 5'-iododeoxyuridine

    The authors review studies of the use of iododeoxyuridine (IdUrd) and bromodeoxyuridine as radiosensitizers and attempt to correlate the clinical outcome for patients treated with radiation and IdUrd with the extent of halogenated pyrimidine cellular uptake and incorporation. (U.K.)

  5. The pyrimidine nucleotide biosynthetic pathway modulates production of biofilm determinants in Escherichia coli.

    Marco Garavaglia

    Full Text Available Bacteria are often found in multicellular communities known as biofilms, which constitute a resistance form against environmental stresses. Extracellular adhesion and cell aggregation factors, responsible for bacterial biofilm formation and maintenance, are tightly regulated in response to physiological and environmental cues. We show that, in Escherichia coli, inactivation of genes belonging to the de novo uridine monophosphate (UMP biosynthetic pathway impairs production of curli fibers and cellulose, important components of the bacterial biofilm matrix, by inhibiting transcription of the csgDEFG operon, thus preventing production of the biofilm master regulator CsgD protein. Supplementing growth media with exogenous uracil, which can be converted to UMP through the pyrimidine nucleotide salvage pathway, restores csgDEFG transcription and curli production. In addition, however, exogenous uracil triggers cellulose production, particularly in strains defective in either carB or pyrB genes, which encode enzymes catalyzing the first steps of de novo UMP biosynthesis. Our results indicate the existence of tight and complex links between pyrimidine metabolism and curli/cellulose production: transcription of the csgDEFG operon responds to pyrimidine nucleotide availability, while cellulose production is triggered by exogenous uracil in the absence of active de novo UMP biosynthesis. We speculate that perturbations in the UMP biosynthetic pathways allow the bacterial cell to sense signals such as starvation, nucleic acids degradation, and availability of exogenous pyrimidines, and to adapt the production of the extracellular matrix to the changing environmental conditions.

  6. ESR study of radiation damage in pyrimidines. Progress report, August 1, 1975--April 1, 1976

    Benson, B.W.

    1976-04-01

    The primary objective of this project is to develop general mechanisms for radiation damage to biomolecules using substituted pyrimidines as a model system. Results this year include a single crystal ESR study of 5-ethyl-5-isopropylbarbituric acid, development of the k-band microwave bridge, dose response measurements on methylated barbituric acid derivatives, and synthesis of several specifically deuterated uracil derivatives.

  7. ESR study of radiation damage in pyrimidines. Progress report, August 1, 1975--April 1, 1976

    The primary objective of this project is to develop general mechanisms for radiation damage to biomolecules using substituted pyrimidines as a model system. Results this year include a single crystal ESR study of 5-ethyl-5-isopropylbarbituric acid, development of the k-band microwave bridge, dose response measurements on methylated barbituric acid derivatives, and synthesis of several specifically deuterated uracil derivatives

  8. A General Regioselective Approach to 2,4-Disubstituted Pyrimidin-5-yl C-2-Deoxyribonucleosides

    Kubelka, Tomáš; Slavětínská, Lenka; Hocek, Michal

    2012-01-01

    Roč. 44, č. 6 (2012), s. 953-965. ISSN 0039-7881 R&D Projects: GA MŠk LC512; GA AV ČR IAA400550902 Institutional research plan: CEZ:AV0Z40550506 Keywords : nucleosides * pyrimidines * cross-coupling * Heck reaction Subject RIV: CC - Organic Chemistry Impact factor: 2.500, year: 2012

  9. The photochemistry of pyrimidine in realistic astrophysical ices and the production of nucleobases

    Nucleobases, together with deoxyribose/ribose and phosphoric acid, are the building blocks of DNA and RNA for all known life. The presence of nucleobase-like compounds in carbonaceous chondrites delivered to the Earth raises the question of an extraterrestrial origin for the molecules that triggered life on our planet. Whether these molecules are formed in interstellar/protostellar environments, in small parent bodies in the solar system, or both, is currently unclear. Recent experiments show that the UV irradiation of pyrimidine (C4H4N2) in H2O-rich ice mixtures that contain NH3, CH3OH, or CH4 leads to the formation of the pyrimidine-based nucleobases uracil, cytosine, and thymine. In this work, we discuss the low-temperature UV irradiation of pyrimidine in realistic astrophysical ice mixtures containing H2O, CH3OH, and NH3, with or without CH4, to search for the production of nucleobases and other prebiotic compounds. These experiments show the presence of uracil, urea, glycerol, hexamethylenetetramine, small amino acids, and small carboxylic acids in all samples. Cytosine was only found in one sample produced from ices irradiated with a higher UV dose, while thymine was not found in any sample, even after irradiation with a higher UV dose. Results are discussed to evaluate the role of the photochemistry of pyrimidine in the inventory of organic molecules detected in meteorites and their astrophysical/astrobiological implications.

  10. X-ray photodesorption and proton destruction in protoplanetary disks: pyrimidine

    Mendoza, E; Andrade, D P P; Luna, H; Wolff, W; Rocco, M L M; Boechat-Roberty, H M

    2013-01-01

    The organic compounds HCN and C2H2, present in protoplanetary disks, may react to form precursor molecules of the nucleobases, such as the pyrimidine molecule, C4H4N2. Depending on the temperature in a given region of the disk, molecules are in the gas phase or condensed onto grain surfaces. The action of X-ray photons and MeV protons, emitted by the young central star, may lead to several physical and chemical processes in such prestellar environments. In this work we have experimentally investigated the ionization, dissociation and desorption processes of pyrimidine in the condensed and the gas phase stimulated by soft X-rays and protons, respectively. Pyrimidine was frozen at temperatures below 130 K and irradiated with X-rays at energies from 394 to 427 eV. In the gas phase experiment, a pyrimidine effusive jet at room temperature was bombarded with protons of 2.5 MeV. In both experiments, the time-of-flight mass-spectrometry technique was employed. Partial photodesorption ion yields as a function of the ...

  11. Formation of Nucleobases from the UV Irradiation of Pyrimidine in Astrophysical Ice Analogs

    Sandford, Scott A.; Nuevo, Michel; Materese, Christopher K.

    2014-01-01

    Nucleobases are the informational subunits of DNA and RNA. They consist of Nheterocycles that belong to either the pyrimidine-base group (uracil, cytosine, and thymine) or the purinebase group (adenine and guanine). Several nucleobases, mostly purine bases, have been detected in meteorites [1-3], with isotopic signatures consistent with an extraterrestrial origin [4]. Uracil is the only pyrimidine-base compound formally reported in meteorites [2], though the presence of cytosine cannot be ruled out [5,6]. However, the actual process by which the uracil was made and the reasons for the non-detection of thymine in meteorites have yet to be fully explained. Although no N-heterocycles have ever been observed in the ISM [7,8], the positions of the 6.2-µm interstellar emission features suggest a population of such molecules is likely to be present [9]. In this work we study the formation of pyrimidine-based molecules, including the three nucleobases uracil, cytosine, and thymine from the ultraviolet (UV) irradiation of pyrimidine in ices consisting of several combinations of H(sub2)O, NH(sub3), CH(sub3)OH, and CH(sub4) at low temperature, in order to simulate the astrophysical conditions under which prebiotic species may be formed in the interstellar medium, in the protosolar nebula, and on icy bodies of the Solar System.

  12. Regulation of Salmonella typhimurium pyr Gene Expression: Effect of Changing Both Purine and Pyrimidine Nucleotide Pools

    Jensen, Kaj Frank

    1989-01-01

    permit manipulation of the intracellular pools of both pyrimidine and purine nucleotides. The results identify the effectory purine compound as being a guanine nucleotide; it is probably GTP, but it may be GDP or GMP. The synthesis of carbamoylphosphate synthase, encoded by pyrA, and particularly...

  13. Excited States of Proton-bound DNA/RNA Base Homo-dimers: Pyrimidines

    Féraud, Géraldine; Dedonder, Claude; Jouvet, Christophe; Pino, Gustavo A

    2015-01-01

    We are presenting the electronic photo fragment spectra of the protonated pyrimidine DNA bases homo-dimers. Only the thymine dimer exhibits a well structured vibrational progression, while protonated monomer shows broad vibrational bands. This shows that proton bonding can block some non radiative processes present in the monomer.

  14. Effect of pressure on heterocyclic compounds: Pyrimidine and s-triazine

    We have examined the high-pressure behaviors of six-membered heterocyclic compounds of pyrimidine and s-triazine up to 26 and 26.5 GPa, respectively. Pyrimidine crystallizes in Pna21 symmetry (phase I) with the freezing pressure of 0.3 GPa, and transforms to another phase (phase II) at 1.1 GPa. Raman spectra of several compression-decompression cycles demonstrate there is a critical pressure of 15.5 GPa for pyrimidine. Pyrimidine returns back to its original liquid state as long as the highest pressure is below 15.1 GPa. Rupture of the aromatic ring is observed once pressure exceeds 15.5 GPa during a compression-decompression cycle, evidenced by the amorphous characteristics of the recovered sample. As for s-triazine, the phase transition from R-3c to C2/c is well reproduced at 0.6 GPa, in comparison with previous Raman data. Detailed Raman scattering experiments corroborate the critical pressure for s-triazine may locate at 14.5 GPa. That is, the compression is reversible below 14.3 GPa, whereas chemical reaction with ring opening is detected when the final pressure is above 14.5 GPa. During compression, the complete amorphization pressure for pyrimidine and s-triazine is identified as 22.4 and 15.2 GPa, respectively, based on disappearance of Raman lattice modes. Synchrotron X-ray diffraction patterns and Fourier transform infrared spectra of recovered samples indicate the products in two cases comprise of extended nitrogen-rich amorphous hydrogenated carbon (a-C:H:N)

  15. Effect of pressure on heterocyclic compounds: Pyrimidine and s-triazine

    Li, Shourui; Li, Qian; Li, Wenbo; Cui, Wen; Liu, Ran; Liu, Bingbing; Zou, Bo, E-mail: zoubo@jlu.edu.cn [State Key Laboratory of Superhard Materials, Jilin University, Changchun 130012 (China); Xiong, Lun; Li, Xiaodong; Liu, Jing [Beijing Synchrotron Radiation Laboratory, Institute of High Energy Physics, Chinese Academy of Sciences, Beijing 100039 (China); Yang, Ke [Shanghai Synchrotron Radiation Facilities, Shanghai Institute of Applied Physics, Chinese Academy of Sciences, Shanghai 201204 (China)

    2014-09-21

    We have examined the high-pressure behaviors of six-membered heterocyclic compounds of pyrimidine and s-triazine up to 26 and 26.5 GPa, respectively. Pyrimidine crystallizes in Pna2{sub 1} symmetry (phase I) with the freezing pressure of 0.3 GPa, and transforms to another phase (phase II) at 1.1 GPa. Raman spectra of several compression-decompression cycles demonstrate there is a critical pressure of 15.5 GPa for pyrimidine. Pyrimidine returns back to its original liquid state as long as the highest pressure is below 15.1 GPa. Rupture of the aromatic ring is observed once pressure exceeds 15.5 GPa during a compression-decompression cycle, evidenced by the amorphous characteristics of the recovered sample. As for s-triazine, the phase transition from R-3c to C2/c is well reproduced at 0.6 GPa, in comparison with previous Raman data. Detailed Raman scattering experiments corroborate the critical pressure for s-triazine may locate at 14.5 GPa. That is, the compression is reversible below 14.3 GPa, whereas chemical reaction with ring opening is detected when the final pressure is above 14.5 GPa. During compression, the complete amorphization pressure for pyrimidine and s-triazine is identified as 22.4 and 15.2 GPa, respectively, based on disappearance of Raman lattice modes. Synchrotron X-ray diffraction patterns and Fourier transform infrared spectra of recovered samples indicate the products in two cases comprise of extended nitrogen-rich amorphous hydrogenated carbon (a-C:H:N)

  16. Monomerization of pyrimidine dimers in DNA by tryptophan-containing peptides: wavelength dependence

    Tryptophan-containing peptides and proteins can sensitize the monomerization of pyrimidine dimers in ultraviolet-irradiated DNA; photoreactivating enzymes catalyze the light-induced monomerization of pyrimidine dimers in DNA. It has recently been proposed that a variety of tryptophan-containing proteins and peptides might be confused with true photoreactivating enzymes both in vivo and in vitro. We have thus characterized the wavelengths required for the tryptophan-sensitized dimer monomerization to determine if this process is distinguishable from true enzymatic photoreactivation. We find that 313-nm radiation can monomerize pyrimidine dimers in DNA in the presence of the peptide lysyl-tryptophyl-lysine; however, 334- 365-, and 405-nm radiation are ineffective for fluences up to 1 MJ/m2. In contrast, each of these wavelengths is capable of monomerizing dimers in the presence of photoreactivating enzymes. Indeed, 334 and 365 nm are always more effective than 313-nm radiation in the case of true enzymatic photoreactivation. The inability of wavelengths other than those near 300 nm to drive the tryptophan-mediated reaction efficiently is consistent with recently reported spectroscopic experiments. The extreme differences in the wavelength specificities for true enzymatic photoreactivation and tryptophan-sensitized monomerization mean that it is easy to differentiate experimentally between the two phenomena. Consideration of the spectral distributions of conventional sources of photoreactivating light indicate that it is extremely unlikely that any of them could contain significant intensities of the wavelengths required for efficient tryptophan-sensitized monomerization of pyrimidine dimers. We thus conclude that tryptophan-sensitized monomerization cannot account for the disappearance of pyrimidine dimers from DNA in cells or cell extracts exposed to photoreactivating light

  17. Issues in Data Labelling

    Cowie, Roddy; Cox, Cate; Martin, Jeam-Claude; Batliner, Anton; Heylen, Dirk; Karpouzis, Kostas; Cowie, Roddy; Pelachaud, Catherine; Petta, Paolo

    2011-01-01

    Labelling emotion databases is not a purely technical matter. It is bound up with theoretical issues. Different issues affect labelling of emotional content, labelling of the signs that convey emotion, and labelling of the relevant context. Linked to these are representational issues, involving time

  18. 5-(1-Substituted) alkyl pyrimidine nucleosides as antiviral (herpes) agents.

    Kumar, Rakesh

    2004-10-01

    The treatment of viral diseases remains one of the major challenges to modern medicine. During the past two decades there has been increased recognition of the consequences of serious viral illnesses that are not controlled by vaccination. These illnesses include human immunodeficiency virus, human herpes viruses, and viruses that cause hepatitis. There are now eight pathogens recognized in the herpes virus family that cause infections in humans. Infections by the herpes viruses are opportunistic and often life-threatening, leading to significant morbidity and mortality in the increasing number of chronically immune compromised individuals such as AIDS patients, cancer patients and transplant recipients on immunosuppressive therapy. Nearly all individuals with AIDS are infected with one or more of the herpes viruses. Antiviral therapy with guanosine nucleoside analogs acyclovir and ganciclovir has had a major impact on diseases caused by herpes simplex virus type-1 and type-2 (HSV-1, HSV-2), Varicella zoster virus (VZV), and human cytomegalovirus (HCMV) but development of resistant virus strains and the absence of any effective treatment for other members of the herpes family provide a stimulus for increased search of new agents effective against various herpes viruses. Pyrimidine nucleosides have taken up an important role in the therapy of virus infection. Significant progress in the study of anti-herpes nucleosides has been made by the advent of 5-substituted pyrimidine nucleosides such as 5-iodo-, 5-ethyl-, 5-(2-chloroethyl)-, and (E)-5-(2-bromovinyl)- derivatives of 2'-deoxyuridine. These are highly specific inhibitors of HSV-1, HSV-2, and/or VZV infections. However, Epstein Barr virus (EBV) and HCMV are much less sensitive to these agents. In 5-substituted pyrimidine nucleosides the nature of substituents, particularly at the C-5 position, has been found to be an important determinant of anti-herpes activity. Structural requirements at the C-2 carbon of the 5

  19. Purification, crystallization and preliminary X-ray diffraction study on pyrimidine nucleoside phosphorylase TTHA1771 from Thermus thermophilus HB8

    Shimizu, Katsumi; Kunishima, Naoki

    2007-01-01

    The pyrimidine nucleoside phosphorylase TTHA1771 from T. thermophilus HB8 has been overexpressed, purified and crystallized. The crystals diffract X-rays to 1.8 Å resolution using synchrotron radiation.

  20. Activity of novel acyclic pyrimidine nucleoside phosphonates against different DNA polymerase mutants of herpes simplex virus type 1 (HSV-1)

    Andrei, G.; Holý, Antonín; Fiten, P.; Opdenakker, G.; De Clercq, E.; Snoeck, R.

    Chicago, 2003. s. 490. [Interscience Conference on Antimicrobial Agents and Chemotherapy /43./. 14.09.2003-17.09.2003, Chicago] Institutional research plan: CEZ:AV0Z4055905 Keywords : pyrimidine nucleoside phosphonates Subject RIV: CC - Organic Chemistry

  1. Synthesis, Structural Studies and Antitumoral Evaluation of C-6 Alkyl and Alkenyl Side Chain Pyrimidine Derivatives S

    Marijeta Kralj

    2009-11-01

    Full Text Available The synthetic route for introduction of fluorophenylalkyl (compounds 5, 7, 14 and 15 and fluorophenylalkenyl (compounds 4E and 13 side chains at C-6 of the pyrimidine nucleus involved the lithiation of the pyrimidine derivatives 1, 2 and 11 and subsequent nucleophilic addition or substitution reactions of the organolithium intermediate thus obtained with 2-fluorophenylacetone, 4-fluoroacetophenone or ethyl 4-fluorobenzoate as electrophiles. The structures of novel compounds were confirmed by 1H-, 19F- and 13C-NMR and MS. Compounds 8 and 10 containing unsaturated fluorophenylalkyl side chains showed better inhibitory effect than their saturated fluorophenylalkylated pyrimidine counterparts 7 and 9. A conformational study based on NOE enhancements showed the importance of the double bond and substitution in the side chain for the conformational preferences in relation to inhibitory activity. Among all tested compounds, C-5 furyl (12 and phenyl (13 and 15 substituted pyrimidine derivatives showed significant cytostatic activities against all tested tumor cell lines.

  2. Poly[bis(methanol-κOtris(μ-pyrimidine-κ2N:N′tetrakis(thiocyanato-κNdinickel(II

    Mario Wriedt

    2009-04-01

    Full Text Available In the crystal structure of the title compound, [Ni2(NCS4(C4H4N23(CH3OH2]n, each nickel(II cation is coordinated by three N-bonded pyrimidine ligands, two N-bonded thiocyanate anions and one O-bonded methanol molecule in a distorted octahedral environment. The asymmetric unit consists of one nickel cation, two thiocyanate anions and one methanol molecule in general positions, as well as one pyrimidine ligand located around a twofold rotation axis. The crystal structure consists of μ-N:N′ pyrimidine-bridged zigzag-like nickel thiocyanate chains; these are further linked by μ-N:N-bridging pyrimidine ligands into layers which are stacked perpendicular to the b axis. The layers are connected via weak O—H...S hydrogen bonding.

  3. Succesful labelling schemes

    Juhl, Hans Jørn; Stacey, Julia

    2001-01-01

    It is usual practice to evaluate the success of a labelling scheme by looking at the awareness percentage, but in many cases this is not sufficient. The awareness percentage gives no indication of which of the consumer segments that are aware of and use labelling schemes and which do not. In the...... spring of 2001 MAPP carried out an extensive consumer study with special emphasis on the Nordic environmentally friendly label 'the swan'. The purpose was to find out how much consumers actually know and use various labelling schemes. 869 households were contacted and asked to fill in a questionnaire....... 664 households returned a completed questionnaire. There were five answering categories for each label in the questionnaire: * have not seen the label before. * I have seen the label before but I do not know the precise contents of the labelling scheme. * I have seen the label before, I do not know...

  4. Analgesic Activity of Some 1,2,4-Triazole Heterocycles Clubbed with Pyrazole, Tetrazole, Isoxazole and Pyrimidine

    Ramdas Bhanudas Pandhare; Popat Baban Mohite; Appala Raju; Shantaram Gajanan Khanage

    2013-01-01

    Purpose: In the present study in vivo analgesic activity of some previously synthesized 1,2,4-triazole derivatives containing pyrazole, tetrazole, isoxazole and pyrimidine ring have been evaluated. Methods: Acetic acid induced writhing method and Hot plate method has been described to study analgesic activity of some 1,2,4-triazole derivatives containing pyrazole, tetrazole, isoxazole and pyrimidine as a pharmacological active lead. Results: Thirty six different derivatives con...

  5. Tandem Aldol-Michael Reactions in Aqueous Diethylamine Medium: A Greener and Efficient Approach to Bis-Pyrimidine Derivatives

    Al-Majid, Abdullah M.; Assem Barakat; Hany J. AL-Najjar; Mabkhot, Yahia N.; Ghabbour, Hazem A.; Hoong-Kun Fun

    2013-01-01

    A simple protocol, involving the green synthesis for the construction of novel bis-pyrimidine derivatives, 3a–i and 4a–e are accomplished by the aqueous diethylamine media promoted tandem Aldol-Michael reaction between two molecules of barbituric acid derivatives 1a,b with various aldehydes. This efficient synthetic protocol using an economic and environmentally friendly reaction media with versatility and shorter reaction time provides bis-pyrimidine derivatives with high yields (88%–99%)....

  6. Tandem aldol-Michael reactions in aqueous diethylamine medium: a greener and efficient approach to bis-pyrimidine derivatives.

    Al-Majid, Abdullah M; Barakat, Assem; Al-Najjar, Hany J; Mabkhot, Yahia N; Ghabbour, Hazem A; Fun, Hoong-Kun

    2013-01-01

    A simple protocol, involving the green synthesis for the construction of novel bis-pyrimidine derivatives, 3a-i and 4a-e are accomplished by the aqueous diethylamine media promoted tandem Aldol-Michael reaction between two molecules of barbituric acid derivatives 1a,b with various aldehydes. This efficient synthetic protocol using an economic and environmentally friendly reaction media with versatility and shorter reaction time provides bis-pyrimidine derivatives with high yields (88%-99%). PMID:24317435

  7. The Photochemistry of Pyrimidine in Pure H2O Ice Subjected to Different Radiation Environments and the Formation of Uracil

    Nuevo, M.; Chen, Y.-J.; Materese. C. K..; Hu, W.-J.; Qiu, J.-M.; Wu, S.-R.; Fung, H.-S.; Sandford, S. A.; Chu, C.-C.; Yih, T.-S.; Wu, R.; Ip, W.-H.

    2013-01-01

    Nucleobases are N-heterocycles which are the informational subunits of DNA and RNA. They include pyrimidine bases (uracil, cytosine, and thymine) and purine bases (adenine and guanine). Nucleobases have been detected in several meteorites, although no Nheterocycles have been observed in space to data. Laboratory experiments showed that the ultraviolet (UV) irradiation of pyrimidine in pure H2O ice at low temperature (function of the photon energy.

  8. Targeting DNA with "light-up" pyrimidine triple-helical forming oligonucleotides conjugated to stabilizing fluorophores (LU-TFOs).

    Renard, Brice-Loïc; Lartia, Rémy; Asseline, Ulysse

    2008-12-01

    The synthesis of triple-helix-forming oligonucleotides (TFOs) linked to a series of cyanine monomethines has been performed. Eight cyanines including one thiocyanine, four thiazole orange analogues, and three quinocyanines were attached to the 5'-end of 10-mer pyrimidine TFOs. The binding properties of these modified TFOs with their double-stranded DNA target were studied by absorption and steady-state fluorescence spectroscopy. The stability of the triplex structures depended on the cyanine structure and the linker size used to connect both entities. The most efficient cyanines able to stabilize the triplex structures, when attached at the 5'-end of the TFO, have been incorporated at both ends and provided triplex structures with increased stability. Fluorescence studies have shown that for the TFOs involving one cyanine, an important intensity increase (up to 37-fold) in the fluorescent signal was observed upon their hybridization with the double-stranded target, proving hybridization. The conjugates involving thiazole orange attached by the benzothiazole ring provided the most balanced properties in terms of triplex stabilization, fluorescence intensity and fluorescence enhancement upon hybridization with the double-stranded target. In order to test the influence of different parameters such as the TFO sequence and length, thiazole orange was used to label 17-mer TFOs. Hybridizations of these TFOs with different duplexes, designed to study the influence of mismatches at both internal and terminal positions on the triplex structures, confirmed the possibility of triplex formation without loss of specificity together with a strong fluorescence enhancement (up to 13-fold). PMID:19005602

  9. Synthesizing labeled compounds

    A metabolic study is presented of the chemical reactions provided by isotopic labeling and NMR spectroscopy. Synthesis of 13C-labeled D-glucose, a 6-carbon sugar, involves adding a labeled nitrile group to the 5-carbon sugar D-arabinose by reaction with labeled hydrogen cyanide. The product of this reaction is then reduced and hydrolyzed to a mixture of the labeled sugars. The two sugars are separated by absorption chromotography. The synthesis of 13C-labeled L-tyrosine, an amino acid, is also presented

  10. Excision of pyrimidine dimers from nuclear deoxyribonucleic acid in ultraviolet-irradiated Dictyostelium discoideum

    Clark, J.M.; Deering, R.A.

    1987-02-01

    A sensitive endonuclease assay was used to study the fate of pyrimidine dimers introduced by ultraviolet irradiation into the nuclear deoxyribonucleic acid of the cellular slime mold Dictyostellium discoideum. Analysis of the frequency of T4 endonuclease V-induced single-strand breaks by alkaline sucrose gradient sedimentation showed that strain NC4 (rad/sup +/) removed >98% of the dimers induced by irradiation at 40 J/m/sup 2/ (254 nm) within 215 min after irradiation. HPS104 (radC44), a mutant sensitive to ultraviolet irradiation, removed 91% under these conditions, although at a significantly slower rate than NC4: only 8% were removed during the 10- to 15- min period immediately after irradiation, whereas NC4 excised 64% during this interval. HPS104 thus appears to be deficient in the activity(ies) responsible for rapidly incising ultraviolet-irradiated nuclear deoxyribonucleic acid at the sites of pyrimidine dimers.

  11. Repair of pyrimidine dimer ultraviolet light photoproducts by human cell extracts

    A newly developed method allows human cell extracts to carry out repair synthesis on ultraviolet light irradiated closed circular plasmid DNA. The identity of the photodamage that leads to this repair replication was investigated. Removal of stable pyrimidine hydrates from irradiated plasmid pAT153 did not significantly affect the amount of repair replication in the fluence range of 0-450 J/m2, because of the low yield of these products and their short DNA repair patch size. Photoreactivation of irradiated DNA using purified Escherichia coli DNA photolyase to remove more than 95% of the cyclobutane dimers from the DNA reduced the observed repair synthesis by 20-40%. The greater part of the repair synthesis is highly likely to be caused by (6-4) pyrimidine dimer photoproducts. This class of lesions is rapidly repaired by mammalian cells, and their removal is known to be important for cell survival after ultraviolet irradiation

  12. [Determination of individual purine and pyrimidine bases in carbohydrate-rich food].

    Lassek, E; Montag, A

    1987-05-01

    The following method was developed for the qualitative and quantitative determination of purine and pyrimidine bases in carbohydrate rich food: The bases were liberated from nucleic acids, nucleotides or nucleosides by acid hydrolysis in a pressure digestion vessel. A complete liberation without losses of purine bases occurs upon hydrolysis for 15 min at 240 degrees C with trifluoroacetic and formic acids (1+1; V + V), pyrimidine bases need 45 min at 240 degrees C. The products arising from side reactions (such as hydroxymethylfurfural from hexoses and furfural from pentoses) could be removed from the hydrolysate by extraction with dichlormethane. The liberated bases could be separated upon stepwise elution by cation exchange chromatography. They were detected and determined by UV-measurements, continuously monitoring at lambda = 260 nm, and integrating electronically. The evaluation was carried out by a method with internal standard. PMID:3604458

  13. Fluorescence properties of metal complexes of 2-N-Anilino pyrimidine

    2-N-Anilino pyrimidine was used as specific binder towards selected transition metals ion such as Mn (II), Ni (II) and Cr (II) in a 1:2 ratio (metal: ligand) to give their respective complexes. The structures of the ligand and complexes were confirmed by spectroscopic analysis. Fluorescence studies of metal complexes of 2-N-Anilino pyrimidine and the ligand itself were carried out under various conditions using methanol as the solvent. In general, metal ions, especially paramagnetic ions, are able to quench the fluorescence of organic ligands. The fluorescence intensity was studied based on several factors such as pH, capped and uncapped conditions. The compounds showed higher intensity in capped samples compared to uncapped samples. (author)

  14. cis-Aquadichlorido[pyrimidin-2(1H-one-κN3]copper(II

    A. Guy Orpen

    2008-07-01

    Full Text Available In the title compound, [CuCl2(C4H4N2O(H2O], the CuII cation is coordinated by two chloride anions, one pyrimidin-2-one N atom and one water molecule, giving a slightly distorted square-planar geometry. In the crystal structure, the pyrimidin-2-one rings stack along the b axis, with an interplanar distance of 3.306 Å, as do the copper coordination planes (interplanar spacing = 2.998 Å. The coordination around the Jahn–Teller-distorted CuII ion is completed by long Cu...O [3.014 (5 Å] and Cu...Cl [3.0194 (15 Å] interactions with adjacent molecules involved in this stacking. Several N—H...Cl, O—H...Cl and O—H...O intermolecular hydrogen bonds form a polar three-dimensional network.

  15. Mental Labels and Tattoos

    Hyatt, I. Ralph

    1977-01-01

    Discusses the ease with which mental labels become imprinted in our system, six basic axioms for maintaining negative mental tattoos, and psychological processes for eliminating mental tattoos and labels. (RK)

  16. Pesticide Product Label System

    U.S. Environmental Protection Agency — The Pesticide Product Label System (PPLS) provides a collection of pesticide product labels (Adobe PDF format) that have been approved by EPA under Section 3 of the...

  17. Dynamics and mechanism of cyclobutane pyrimidine dimer repair by DNA photolyase

    Liu, Zheyun; Tan, Chuang; Guo, Xunmin; Kao, Ya-Ting; Li, Jiang; Wang, Lijuan; Sancar, Aziz; Zhong, Dongping

    2011-01-01

    Photolyase uses blue light to restore the major ultraviolet (UV)-induced DNA damage, the cyclobutane pyrimidine dimer (CPD), to two normal bases by splitting the cyclobutane ring. Our earlier studies showed that the overall repair is completed in 700 ps through a cyclic electron-transfer radical mechanism. However, the two fundamental processes, electron-tunneling pathways and cyclobutane ring splitting, were not resolved. Here, we use ultrafast UV absorption spectroscopy to show that the CPD...

  18. Use of cyanoethyl protective group in synthesis of N1 alkylated pyrimidines

    Bernášková, Markéta; Holý, Antonín; Pohl, Radek

    Marburg : University of Marburg, 2006. s. 112. ISBN 3-89703-685-1. [Joint Meeting of the Czech, German and Hungarian Pharmaceutical Societies. 04.10.2006-07.10.2006, Marburg] R&D Projects: GA MŠk(CZ) 1M0508 Grant ostatní: Descartes Prize(XE) HPAW-2002-100096 Institutional research plan: CEZ:AV0Z40550506 Keywords : cyanoethyl protective group * pyrimidines Subject RIV: CC - Organic Chemistry

  19. Targeting one carbon metabolism with an antimetabolite disrupts pyrimidine homeostasis and induces nucleotide overflow

    Ser, Zheng; GAO, XIA; Johnson, Christelle; Mehrmohamadi, Mahya; Liu, Xiaojing; Li, SiQi; Locasale, Jason W.

    2016-01-01

    Anti-metabolite agents that affect nucleotide metabolism are frontline chemotherapy agents in several cancers and often successfully target one carbon metabolism. However, the precise mechanisms and resulting determinants of their therapeutic value are unknown. We show that 5-fluorouracil (5-FU), a commonly used anti-metabolite therapeutic with varying efficacy, induces specific alterations to nucleotide metabolism by disrupting pyrimidine homeostasis. An integrative metabolomics analysis of ...

  20. An Efficient Four-Component,One-Pot Synthesis of Poly-Substituted Pyrimidines in Water

    WANG,Zhongqing; GE,Zemei; CHENG,Tieming; LI,Runtao

    2009-01-01

    An efficient environmentally friendly synthesis of poly-substituted pyrimidines has been developed via a four-component,one-pot reaction of malononitrile,carbon disulfide,alkyl halide and S-alkylisothiouronium salt in water at room temperature.Water as solvent,mild reaction conditions,short reaction time,simple experimental procedures,broad scope of substrates and good yields are the main advantages of this method.

  1. SYNTHESIS, CHARACTERIZATION AND CHELATING PROPERTIES OF PYRIMIDINE-QUINOLINE COMBINED MOLECULE WITH TRANSITION METALS

    Purvesh J. Shah

    2013-09-01

    Full Text Available The treatment of ethyl-6-methyl-2-oxo-4-phenyl-1,2-dihydropyrimidone-5-carboxylate with 5-amino-8-hydroxyquinoline afford a N-(4-hydroxyquinolin-5-yl-6-methyl-2-oxo-4-phenyl-1,2-dihydro pyrimidine-5-carboxamide(PDHQ. The transition metal complexes of Cu2+,Co2+ ,Ni2+, Mn2+ and Zn2+ of PDHQ have been prepared and characterized by elemental analysis, spectral studies, magnetic moment determination, molar conductivity measurement and microbicidal activity.

  2. How study patients who receive fluo pyrimidines to prevent ischemic events

    Introduction: Ischemic heart disease is the main cause of death in Uruguay and cancer is the second. The pillar of the systemic treatment of colorectal cancer are fluo pyrimidines and cause acute ischemic events in 3-8% of t rated patients. The 5 fluorouracil is the third anticancer drug most used Objective: Due to the high incidence of the two diseases and the risk of death caused by the ischemic treatment complications, the literature is analyzed to define how to study patients who receive fluo pyrimidines as a medium of preventing the same. Development: fluo pyrimidines cardio-toxicity can occur by myocardial toxicity, vasospasm, dihydropyrimidine dehydrogenase deficiency, autoimmune phenomena, platelet hyper aggregability, etc. The clinic is varied and underestimated: angina, abnormal ST silent and reversible, arrhythmias, heart failure, hypertension and heart failure. It is the most common complication with continuous infusion of 5 Fu and its equivalent capecitabine with bolus f lou pyrimidines. It is common that ischemic heart disease prioritises the risk increase of complications, but their absence does not exist. Without ischemic heart disease it is difficult to prevent ischemic events, however proposes that the older higher risk. Results: No uniform guidelines is advised: detailed history, determine if risk factors such as smoking, hypertension, diabetes and dyslipidemia and They are present electrocardiogram and cardiac evaluation. Warn the patient about angina l pain as early symptom and monitor symptoms during chemotherapy including cardio-vascular hypotension. Discontinue the medication and perform classic anti-angina l symptoms and / or signs of ischemia. Not reintroduce unless it is the only therapeutic option, since mortality may exceed

  3. Triazole pyrimidine nucleosides as inhibitors of Ribonuclease A. Synthesis, biochemical, and structural evaluation.

    Parmenopoulou, Vanessa; Chatzileontiadou, Demetra S M; Manta, Stella; Bougiatioti, Stamatina; Maragozidis, Panagiotis; Gkaragkouni, Dimitra-Niki; Kaffesaki, Eleni; Kantsadi, Anastassia L; Skamnaki, Vassiliki T; Zographos, Spyridon E; Zounpoulakis, Panagiotis; Balatsos, Nikolaos A A; Komiotis, Dimitris; Leonidas, Demetres D

    2012-12-15

    Five ribofuranosyl pyrimidine nucleosides and their corresponding 1,2,3-triazole derivatives have been synthesized and characterized. Their inhibitory action to Ribonuclease A has been studied by biochemical analysis and X-ray crystallography. These compounds are potent competitive inhibitors of RNase A with low μM inhibition constant (K(i)) values with the ones having a triazolo linker being more potent than the ones without. The most potent of these is 1-[(β-D-ribofuranosyl)-1,2,3-triazol-4-yl]uracil being with K(i) = 1.6 μM. The high resolution X-ray crystal structures of the RNase A in complex with three most potent inhibitors of these inhibitors have shown that they bind at the enzyme catalytic cleft with the pyrimidine nucleobase at the B(1) subsite while the triazole moiety binds at the main subsite P(1), where P-O5' bond cleavage occurs, and the ribose at the interface between subsites P(1) and P(0) exploiting interactions with residues from both subsites. The effect of a susbsituent group at the 5-pyrimidine position at the inhibitory potency has been also examined and results show that any addition at this position leads to a less efficient inhibitor. Comparative structural analysis of these RNase A complexes with other similar RNase A-ligand complexes reveals that the triazole moiety interactions with the protein form the structural basis of their increased potency. The insertion of a triazole linker between the pyrimidine base and the ribose forms the starting point for further improvement of these inhibitors in the quest for potent ribonucleolytic inhibitors with pharmaceutical potential. PMID:23122937

  4. Quenching of highly vibrationally excited pyrimidine by collisions with CO2

    Relaxation of highly vibrationally excited pyrimidine (C4N2H4) by collisions with carbon dioxide has been investigated using diode laser transient absorption spectroscopy. Vibrationally hot pyrimidine (E'=40 635 cm-1) was prepared by 248-nm excimer laser excitation, followed by rapid radiationless relaxation to the ground electronic state. The nascent rotational population distribution (J=58-80) of the 0000 ground state of CO2 resulting from collisions with hot pyrimidine was probed at short times following the excimer laser pulse. Doppler spectroscopy was used to measure the CO2 recoil velocity distribution for J=58-80 of the 0000 state. Rate constants and probabilities for collisions populating these CO2 rotational states were determined. The measured energy transfer probabilities, indexed by final bath state, were resorted as a function of ΔE to create the energy transfer distribution function, P(E,E'), from E'-E∼1300-7000 cm-1. P(E,E') is fitted to a single exponential and a biexponential function to determine the average energy transferred in a single collision between pyrimidine and CO2 and parameters that can be compared to previously studied systems using this technique, pyrazine/CO2, C6F6/CO2, and methylpyrazine/CO2. P(E,E') parameters for these four systems are also compared to various molecular properties of the donor molecules. Finally, P(E,E') is analyzed in the context of two models, one which suggests that the shape of P(E,E') is primarily determined by the low-frequency out-of-plane donor vibrational modes and one which suggests that the shape of P(E,E') can be determined by how the donor molecule final density of states changes with ΔE

  5. Arginine and pyrimidine biosynthetic defects in Neisseria gonorrhoeae strains isolated from patients.

    Shinners, E N; Catlin, B W

    1982-01-01

    Neisseria gonorrhoeae strains with nutritional requirements that include arginine (Arg-), uracil (Ura-), and hypoxanthine have attracted attention because of their tendency to cause disseminated infections, as a basis for genetic studies of arginine and pyrimidine biosynthesis, we examined the activities of four enzymes of these pathways in cell-free extracts of both prototrophic and Arg- Ura- strains. Activities of glutamate acetyltransferase, aspartate transcarbamylase, and orotate phosphor...

  6. A study of pyrimidine base damage in relation to oxidative stress and cancer

    Iijima, H.; Patrzyc, H B; Budzinski, E E; Freund, H G; Dawidzik, J B; Rodabaugh, K. J.; Box, H C

    2009-01-01

    Background: A long-standing hypothesis is that oxidative stress is a risk factor for cancer. Support for this hypothesis comes from observations of higher levels of oxidative damage in the DNA of WBC of cancer patients compared with healthy controls. Methods: Two generally overlooked types of DNA damage, the formamide modification and the thymine glycol modification, both derived from pyrimidine bases, were assayed as markers of oxidative stress. Damage levels were measured in the DNA of WBC ...

  7. The photochemistry of pyrimidine in realistic astrophysical ices and the production of nucleobases

    Nuevo, Michel; Materese, Christopher K.; Sandford, Scott A., E-mail: michel.nuevo-1@nasa.gov [NASA Ames Research Center, MS 245-6, Moffett Field, CA 94035 (United States)

    2014-10-01

    Nucleobases, together with deoxyribose/ribose and phosphoric acid, are the building blocks of DNA and RNA for all known life. The presence of nucleobase-like compounds in carbonaceous chondrites delivered to the Earth raises the question of an extraterrestrial origin for the molecules that triggered life on our planet. Whether these molecules are formed in interstellar/protostellar environments, in small parent bodies in the solar system, or both, is currently unclear. Recent experiments show that the UV irradiation of pyrimidine (C{sub 4}H{sub 4}N{sub 2}) in H{sub 2}O-rich ice mixtures that contain NH{sub 3}, CH{sub 3}OH, or CH{sub 4} leads to the formation of the pyrimidine-based nucleobases uracil, cytosine, and thymine. In this work, we discuss the low-temperature UV irradiation of pyrimidine in realistic astrophysical ice mixtures containing H{sub 2}O, CH{sub 3}OH, and NH{sub 3}, with or without CH{sub 4}, to search for the production of nucleobases and other prebiotic compounds. These experiments show the presence of uracil, urea, glycerol, hexamethylenetetramine, small amino acids, and small carboxylic acids in all samples. Cytosine was only found in one sample produced from ices irradiated with a higher UV dose, while thymine was not found in any sample, even after irradiation with a higher UV dose. Results are discussed to evaluate the role of the photochemistry of pyrimidine in the inventory of organic molecules detected in meteorites and their astrophysical/astrobiological implications.

  8. Polyamine effects on purine-purine-pyrimidine triple helix formation by phosphodiester and phosphorothioate oligodeoxyribonucleotides.

    Musso, M.; Van Dyke, M. W.

    1995-01-01

    Utilization of oligodeoxyribonucleotides to inhibit specific gene transcription in vivo (antigene strategy) requires the efficient formation of triple helices under physiological conditions. However, pyrimidine-motif triplexes are not favored at physiological pH, and physiological concentrations of potassium cations hamper purine-motif triplex formation. Here we investigated the effects of polyamines on promoting triplex formation by G/T-rich oligodeoxyribonucleotides containing either phosph...

  9. Triplex formation with alpha anomers of purine-rich and pyrimidine-rich oligodeoxynucleotides.

    Noonberg, S B; François, J C; Praseuth, D; Guieysse-Peugeot, A L; Lacoste, J; Garestier, T; Hélène, C

    1995-01-01

    Nuclease-resistant alpha anomers of pyrimidine-rich CT- and purine-rich GA- and GT-containing oligonucleotides were investigated for their triplex-forming potential and compared with their corresponding nuclease-sensitive beta anomers. Both 23mer CT-alpha and 23mer CT-beta had quite similar triplex binding affinities. Synthetic 23mer GT-alpha oligonucleotides were capable of triplex formation with binding affinities slightly lower than corresponding 23mer GT-beta oligonucleotides. The orienta...

  10. An Experimental and Computational Study of the Valence Photoelectron Spectra of Halogenated Pyrimidines

    O'Keeffe, Patrick; Bolognesi, Paola; Casavola, Anna Rita; Catone, Daniele; Zema, Nicola; Turchini, Stefano; Avaldi, Lorenzo

    2009-01-01

    Abstract The electronic structures of pyrimidine and a selection of its halogen substituted derivatives have been investigated using ultraviolet photoelectron spectroscopy and ab initio quantum chemical methods. Assignments are proposed for all of the features in the PES spectra by comparison with the vertical ionisation energies of the molecular orbitals calculated using the partial third order quasiparticle approximation as applied to electron propagator theory and a correct...

  11. Intermediate energy cross sections for electron-impact vibrational-excitation of pyrimidine

    We report differential cross sections (DCSs) and integral cross sections (ICSs) for electron-impact vibrational-excitation of pyrimidine, at incident electron energies in the range 15–50 eV. The scattered electron angular range for the DCS measurements was 15°–90°. The measurements at the DCS-level are the first to be reported for vibrational-excitation in pyrimidine via electron impact, while for the ICS we extend the results from the only previous condensed-phase study [P. L. Levesque, M. Michaud, and L. Sanche, J. Chem. Phys. 122, 094701 (2005)], for electron energies ⩽12 eV, to higher energies. Interestingly, the trend in the magnitude of the lower energy condensed-phase ICSs is much smaller when compared to the corresponding gas phase results. As there is no evidence for the existence of any shape-resonances, in the available pyrimidine total cross sections [Baek et al., Phys. Rev. A 88, 032702 (2013); Fuss et al., ibid. 88, 042702 (2013)], between 10 and 20 eV, this mismatch in absolute magnitude between the condensed-phase and gas-phase ICSs might be indicative for collective-behaviour effects in the condensed-phase results

  12. Steroidal pyrimidines: Synthesis, characterization, molecular docking studies with DNA and in vitro cytotoxicity

    Shamsuzzaman; Dar, Ayaz Mahmood; Yaseen, Zahid; Alam, Khursheed; Hussain, Altaf; Gatoo, Manzoor Ahmad

    2013-08-01

    A series of new steroid pyrimidines (7-9) were synthesized by reacting steroidal thiosemicarbazones (4-6) with diethyl malonate. The new compounds were characterized by IR, 1H NMR, 13C NMR, MS and analytical data. The interaction studies of compounds (7-9) with DNA were carried out by employing gel electrophoresis, UV-vis and fluorescence spectroscopy. The acting force between the compounds (7-9) and DNA was mainly hydrophobic while the other interactions like van der Waals, hydrogen bonding cannot be ruled out. The gel electrophoresis pattern also demonstrated that the compound 7 alone or in presence of Cu (II) causes the nicking of supercoiled pBR322 and it seems to follow the mechanistic pathway involving generation of hydroxyl radicals that are responsible for initiating DNA strand scission. The docking study of compounds (7-9) suggested that the intercalation of compounds in between the nucleotide base pairs might be due to the presence of pyrimidine moiety in steroid molecule. MTT assay was carried out to check the toxicity of new compounds (7-9) against the different human cancer as well as non-cancer cell lines A545, MCF-7, HeLa, HL-60, SW480, HepG2, HT-29, A549, 184B5, MCF10A, NL-20, HPC and HPLF. Apoptotic degradation of DNA in presence of steroidal pyrimidines (7-9) was analyzed by agarose gel electrophoresis and visualized by ethidium bromide staining (comet assay).

  13. Differences in pyrimidine dimer removal between rat skin cells in vitro and in vivo

    Pyrimidine dimers, the most abundant type of DNA lesions induced by ultraviolet light (UV), are rapidly repaired in human skin fibroblasts in vitro. In the same cell type from rats, however, there is hardly any removal of such dimers. To investigate whether this low capacity of rat skin cells to repair lesions in their DNA is an inherent characteristic of this species or an artifact due to cell culturing, we measured the removal of UV-induced pyrimidine dimers from rat epidermal keratinocytes both in vitro and in vivo. Epidermal keratinocytes in vitro were unable to remove any dimers over the first 3 h after UV-irradiation, while only about 20% was removed during a repair period of 24 h. In this respect, these cells were not different from cultured rat fibroblasts. In contrast to the results obtained with keratinocytes in vitro, we observed a rapid repair of pyrimidine dimers in UV-irradiated keratinocytes in vivo over the first 3 h; this rapid repair phase was followed by a much slower repair phase between 3 and 24 h. These results are discussed in terms of the possibility that mammalian cells are able to switch from one DNA repair pathway to another

  14. Insights into the pyrimidine biosynthetic pathway of human malaria parasite Plasmodium falciparum as chemotherapeutic target.

    Krungkrai, Sudaratana R; Krungkrai, Jerapan

    2016-06-01

    Malaria is a major cause of morbidity and mortality in humans. Artemisinins remain as the first-line treatment for Plasmodium falciparum (P. falciparum) malaria although drug resistance has already emerged and spread in Southeast Asia. Thus, to fight this disease, there is an urgent need to develop new antimalarial drugs for malaria chemotherapy. Unlike human host cells, P. falciparum cannot salvage preformed pyrimidine bases or nucleosides from the extracellular environment and relies solely on nucleotides synthesized through the de novo biosynthetic pathway. This review presents significant progress on understanding the de novo pyrimidine pathway and the functional enzymes in the human parasite P. falciparum. Current knowledge in genomics and metabolomics are described, particularly focusing on the parasite purine and pyrimidine nucleotide metabolism. These include gene annotation, characterization and molecular mechanism of the enzymes that are different from the human host pathway. Recent elucidation of the three-dimensional crystal structures and the catalytic reactions of three enzymes: dihydroorotate dehydrogenase, orotate phosphoribosyltransferase, and orotidine 5'-monophosphate decarboxylase, as well as their inhibitors are reviewed in the context of their therapeutic potential against malaria. PMID:27262062

  15. Intermediate energy cross sections for electron-impact vibrational-excitation of pyrimidine

    Jones, D. B. [School of Chemical and Physical Sciences, Flinders University, GPO Box 2100, Adelaide, SA 5001 (Australia); Ellis-Gibbings, L.; García, G. [Instituto de Física Fundamental, CSIC, Serrano 113-bis, 28006 Madrid (Spain); Nixon, K. L. [Departamento de Física, Universidade Federal de Juiz de Fora, 36036-330 Juiz de Fora, Minas Gerais (Brazil); School of Biology, Chemistry and Forensic Science, University of Wolverhampton, Wolverhampton WV1 1LY (United Kingdom); Lopes, M. C. A. [Departamento de Física, Universidade Federal de Juiz de Fora, 36036-330 Juiz de Fora, Minas Gerais (Brazil); Brunger, M. J., E-mail: Michael.Brunger@flinders.edu.au [School of Chemical and Physical Sciences, Flinders University, GPO Box 2100, Adelaide, SA 5001 (Australia); Institute of Mathematical Sciences, University of Malaya, 50603 Kuala Lumpur (Malaysia)

    2015-09-07

    We report differential cross sections (DCSs) and integral cross sections (ICSs) for electron-impact vibrational-excitation of pyrimidine, at incident electron energies in the range 15–50 eV. The scattered electron angular range for the DCS measurements was 15°–90°. The measurements at the DCS-level are the first to be reported for vibrational-excitation in pyrimidine via electron impact, while for the ICS we extend the results from the only previous condensed-phase study [P. L. Levesque, M. Michaud, and L. Sanche, J. Chem. Phys. 122, 094701 (2005)], for electron energies ⩽12 eV, to higher energies. Interestingly, the trend in the magnitude of the lower energy condensed-phase ICSs is much smaller when compared to the corresponding gas phase results. As there is no evidence for the existence of any shape-resonances, in the available pyrimidine total cross sections [Baek et al., Phys. Rev. A 88, 032702 (2013); Fuss et al., ibid. 88, 042702 (2013)], between 10 and 20 eV, this mismatch in absolute magnitude between the condensed-phase and gas-phase ICSs might be indicative for collective-behaviour effects in the condensed-phase results.

  16. New Approach for Inhibition of HIV Entry: Modifying CD4 Binding Sites by Thiolated Pyrimidine Derivatives.

    Kanizsai, Szilvia; Ongrádi, József; Aradi, János; Nagy, Károly

    2016-07-01

    Thiolated pyrimidine derivatives have been synthetized and their antiretroviral effect against human immunodeficiency virus type 1 (HIV-1IIIB) and HIV-1 chimeric pseudovirions have been quantitatively determined in cell-based viral infectivity assays including syncytium inhibition assay as well as a single-cycle viral infection assay on HeLaCD4-LTR/ß-gal cells. Pseudotype virions prepared bearing HIV-1 envelope preference for CCR5 coreceptor, CXCR4 coreceptor or for both, respectively, with a HIV-1 core containing luciferase reporter gene were able to infect susceptible cells but are replication defective so unable to replicate in the cells . Data indicate that thiolated pyrimidine derivatives inhibited effectively virally induced cell fusion in vitro as well as infectivity of primary HIV-1IIIB strain and HIV-1 pseudovirions using chemokine receptors CCR5 or CXCR4 or both for virus entry a dose dependent manner. Inhibition was selective, depended on the pseudovirus coreceptor preference. Our results suggest that some of these sulfur containing pyrimidines interact with redoxactive -SH groups required for successful HIV entry, including a redox active disulfide in the CD4 molecule as well as -SH groups in HIV viral envelope gp120. This mode of action is unique representing a new class of potential HIV entry inhibitors. PMID:26860867

  17. Absolute cross sections for electronic excitation of pyrimidine by electron impact

    Regeta, Khrystyna; Allan, Michael [Department of Chemistry, University of Fribourg, Chemin du Musée 9, CH-1700 Fribourg (Switzerland); Mašín, Zdeněk [Max-Born Institute for Nonlinear Optics and Short Pulse Spectroscopy, Max-Born-Straße 2A, 12489 Berlin (Germany); Gorfinkiel, Jimena D. [Department of Physical Sciences, The Open University, Walton Hall, Milton Keynes MK7 6AA (United Kingdom)

    2016-01-14

    We measured differential cross sections for electron-impact electronic excitation of pyrimidine, both as a function of electron energy up to 18 eV, and of scattering angle up to 180°. The emphasis of the present work is on recording detailed excitation functions revealing resonances in the excitation process. The differential cross sections were summed to obtain integral cross sections. These are compared to results of R-matrix calculations, which successfully reproduce both the magnitude of the cross section and the major resonant features. Comparison of the experiment to the calculated contributions of different symmetries to the integral cross section permitted assignment of several features to specific core-excited resonances. Comparison of the resonant structure of pyrimidine with that of benzene revealed pronounced similarities and thus a dominant role of π–π{sup ∗} excited states and resonances. Electron energy loss spectra were measured as a preparation for the cross section measurements and vibrational structure was observed for some of the triplet states. A detailed analysis of the electronic excited states of pyrimidine is also presented.

  18. On Online Labeling with Polynomially Many Labels

    Babka, Martin; Bulánek, Jan; Cunat, Vladimír; Koucky, Michal; Saks, Michael

    2012-01-01

    In the online labeling problem with parameters n and m we are presented with a sequence of nkeys from a totally ordered universe U and must assign each arriving key a label from the label set {1,2,…,m} so that the order of labels (strictly) respects the ordering on U. As new keys arrive it may be...... necessary to change the labels of some items; such changes may be done at any time at unit cost for each change. The goal is to minimize the total cost. An alternative formulation of this problem is the file maintenance problem, in which the items, instead of being labeled, are maintained in sorted order in...... are known that use O(n logn) relabelings. A matching lower bound was claimed in [7]. That proof involved two distinct steps: a lower bound for a problem they call prefix bucketing and a reduction from prefix bucketing to online labeling. The reduction seems to be incorrect, leaving a (seemingly...

  19. Critical importance of the de novo pyrimidine biosynthesis pathway for Trypanosoma cruzi growth in the mammalian host cell cytoplasm

    Highlights: ► We established Trypanosoma cruzi lacking the gene for carbamoyl phosphate synthetase II. ► Disruption of the cpsII gene significantly reduced the growth of epimastigotes. ► In particular, the CPSII-null mutant severely retarded intracellular growth. ► The de novo pyrimidine pathway is critical for the parasite growth in the host cell. -- Abstract: The intracellular parasitic protist Trypanosoma cruzi is the causative agent of Chagas disease in Latin America. In general, pyrimidine nucleotides are supplied by both de novo biosynthesis and salvage pathways. While epimastigotes—an insect form—possess both activities, amastigotes—an intracellular replicating form of T. cruzi—are unable to mediate the uptake of pyrimidine. However, the requirement of de novo pyrimidine biosynthesis for parasite growth and survival has not yet been elucidated. Carbamoyl-phosphate synthetase II (CPSII) is the first and rate-limiting enzyme of the de novo biosynthetic pathway, and increased CPSII activity is associated with the rapid proliferation of tumor cells. In the present study, we showed that disruption of the T. cruzicpsII gene significantly reduced parasite growth. In particular, the growth of amastigotes lacking the cpsII gene was severely suppressed. Thus, the de novo pyrimidine pathway is important for proliferation of T. cruzi in the host cell cytoplasm and represents a promising target for chemotherapy against Chagas disease.

  20. Critical importance of the de novo pyrimidine biosynthesis pathway for Trypanosoma cruzi growth in the mammalian host cell cytoplasm

    Hashimoto, Muneaki, E-mail: muneaki@juntendo.ac.jp [Department of Molecular and Cellular Parasitology, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421 (Japan); Morales, Jorge; Fukai, Yoshihisa; Suzuki, Shigeo; Takamiya, Shinzaburo; Tsubouchi, Akiko; Inoue, Syou [Department of Molecular and Cellular Parasitology, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421 (Japan); Inoue, Masayuki [Graduate School of Pharmaceutical Sciences, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033 (Japan); Kita, Kiyoshi [Department of Biomedical Chemistry, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033 (Japan); Harada, Shigeharu [Department of Applied Biology, Graduate School of Science and Technology, Kyoto Institute of Technology, Sakyo-ku, Kyoto 606-8585 (Japan); Tanaka, Akiko [Systems and Structural Biology Center, RIKEN, Tsurumi, Yokohama 230-0045 (Japan); Aoki, Takashi [Department of Molecular and Cellular Parasitology, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421 (Japan); Nara, Takeshi, E-mail: tnara@juntendo.ac.jp [Department of Molecular and Cellular Parasitology, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421 (Japan)

    2012-01-20

    Highlights: Black-Right-Pointing-Pointer We established Trypanosoma cruzi lacking the gene for carbamoyl phosphate synthetase II. Black-Right-Pointing-Pointer Disruption of the cpsII gene significantly reduced the growth of epimastigotes. Black-Right-Pointing-Pointer In particular, the CPSII-null mutant severely retarded intracellular growth. Black-Right-Pointing-Pointer The de novo pyrimidine pathway is critical for the parasite growth in the host cell. -- Abstract: The intracellular parasitic protist Trypanosoma cruzi is the causative agent of Chagas disease in Latin America. In general, pyrimidine nucleotides are supplied by both de novo biosynthesis and salvage pathways. While epimastigotes-an insect form-possess both activities, amastigotes-an intracellular replicating form of T. cruzi-are unable to mediate the uptake of pyrimidine. However, the requirement of de novo pyrimidine biosynthesis for parasite growth and survival has not yet been elucidated. Carbamoyl-phosphate synthetase II (CPSII) is the first and rate-limiting enzyme of the de novo biosynthetic pathway, and increased CPSII activity is associated with the rapid proliferation of tumor cells. In the present study, we showed that disruption of the T. cruzicpsII gene significantly reduced parasite growth. In particular, the growth of amastigotes lacking the cpsII gene was severely suppressed. Thus, the de novo pyrimidine pathway is important for proliferation of T. cruzi in the host cell cytoplasm and represents a promising target for chemotherapy against Chagas disease.

  1. Poly purine.pyrimidine sequences upstream of the beta-galactosidase gene affect gene expression in Saccharomyces cerevisiae

    Brahmachari Samir K

    2001-10-01

    Full Text Available Abstract Background Poly purine.pyrimidine sequences have the potential to adopt intramolecular triplex structures and are overrepresented upstream of genes in eukaryotes. These sequences may regulate gene expression by modulating the interaction of transcription factors with DNA sequences upstream of genes. Results A poly purine.pyrimidine sequence with the potential to adopt an intramolecular triplex DNA structure was designed. The sequence was inserted within a nucleosome positioned upstream of the β-galactosidase gene in yeast, Saccharomyces cerevisiae, between the cycl promoter and gal 10Upstream Activating Sequences (UASg. Upon derepression with galactose, β-galactosidase gene expression is reduced 12-fold in cells carrying single copy poly purine.pyrimidine sequences. This reduction in expression is correlated with reduced transcription. Furthermore, we show that plasmids carrying a poly purine.pyrimidine sequence are not specifically lost from yeast cells. Conclusion We propose that a poly purine.pyrimidine sequence upstream of a gene affects transcription. Plasmids carrying this sequence are not specifically lost from cells and thus no additional effort is needed for the replication of these sequences in eukaryotic cells.

  2. Two new Pb coordination polymers derived from pyrimidine-2-thiolate: Synthesis, methyl substitution-induced effect and properties

    Song, Jiang-Feng; Li, Si-Zhe; Zhou, Rui-Sha; Hu, Tuo-Ping; Shao, Jia; Zhang, Xiao

    2016-07-01

    Two new coordination compounds, {Pb(pymt)2}∞ (1) and {Pb(mpymt)2}∞ (2) (pymt = pyrimidine-2-thiolate and mpymt = 4-methyl-pyrimidine-2-thione) have been synthesized under solvothermal conditions and characterized by elemental analyses, IR spectroscopy, thermogravimetric analysis, powder X-ray diffraction and single-crystal X-ray diffraction. In compounds 1 and 2, pymt- and mpymt- adopt the same coordination modes (μ-1 κN, S and μ2-1 κN, S: 2 κS, N) to interacted with Pb2+, however, different topology structures for compounds 1 and 2 are obtained. Compound 1 displays a one-dimensional (1D) ribbon with square cavity constructed from two double concentric chains of [Pb-S]∞ and [Pb-Pyrimidine] ∞ sharing Pb1 ions. Compound 2 shows 1D polymeric single chain constructed by [Pb-S]∞ and [Pb-methyl-pyrimidine]∞ chains. The results revealed that the methyl groups don't influence the coordination modes of pyrimidine-2-thiolate but directed the structural variations. Moreover, the fluorescent properties of compounds 1 and 2 were investigated.

  3. Site-specific labeling of nucleotides for making RNA for high resolution NMR studies using an E. coli strain disabled in the oxidative pentose phosphate pathway

    Escherichia coli (E. coli) is a versatile organism for making nucleotides labeled with stable isotopes (13C, 15N, and/or 2H) for structural and molecular dynamics characterizations. Growth of a mutant E. coli strain deficient in the pentose phosphate pathway enzyme glucose-6-phosphate dehydrogenase (K10-1516) on 2-13C-glycerol and 15N-ammonium sulfate in Studier minimal medium enables labeling at sites useful for NMR spectroscopy. However, 13C-sodium formate combined with 13C-2-glycerol in the growth media adds labels to new positions. In the absence of labeled formate, both C5 and C6 positions of the pyrimidine rings are labeled with minimal multiplet splitting due to 1JC5C6 scalar coupling. However, the C2/C8 sites within purine rings and the C1'/C3'/C5' positions within the ribose rings have reduced labeling. Addition of 13C-labeled formate leads to increased labeling at the base C2/C8 and the ribose C1'/C3'/C5' positions; these new specific labels result in two- to three-fold increase in the number of resolved resonances. This use of formate and 15N-ammonium sulfate promises to extend further the utility of these alternate site specific labels to make labeled RNA for downstream biophysical applications such as structural, dynamics and functional studies of interesting biologically relevant RNAs.

  4. Heteroaromatization with 4-Hydroxycoumarin Part II: Synthesis of Some New Pyrano[2,3-d]pyrimidines, [1,2,4]triazolo[1,5-c]pyrimidines and Pyrimido[1,6-b]-[1,2,4]triazine Derivatives

    A. H. Bedair

    2001-05-01

    Full Text Available A variety of novel [1,2,4]triazolo[1,5-c]pyrimidine-13-ones (4a-f and (5b-d could be obtained via reaction of 9-amino-7-(4’-chlorophenyl-8,9-dihydro-8-imino-6H,7H-[1]benzopyrano[3`,4`:5,6]pyrano[2,3-d]pyrimidine-6-one (3 with a variety of reagents. Pyrano[2,3-d]pyrimidine-6-ones 5a, 8a-c and pyrimido[1,6-b][1,2,4]-triazine-3,14-dione (6 were also prepared. The antimicrobial activity of some of the synthesized compounds was tested.

  5. Deuterium labeled cannabinoids

    Complex reactions involving ring opening, ring closure and rearrangements hamper complete understanding of the fragmentation processes in the mass spectrometric fragmentation patterns of cannabinoids. Specifically labelled compounds are very powerful tools for obtaining more insight into fragmentation mechanisms and ion structures and therefore the synthesis of specifically deuterated cannabinoids was undertaken. For this, it was necessary to investigate the preparation of cannabinoids, appropriately functionalized for specific introduction of deuterium atom labels. The results of mass spectrometry with these labelled cannabinoids are described. (Auth.)

  6. Labelling Fashion Markets

    Aspers, P.

    2008-01-01

    The present article discusses how an ethical and environmental labelling system can be implemented in fashion garment markets. Consumers act in markets that provide them with more information than their limited cognitive capacity allows them to handle. Ethical and environmental labelling in markets characterized by change, such as the fashion garment market, makes decision-making even more complicated. The ethical and environmental labelling system proposed here is designed to alleviate firms...

  7. Blood cell labelling

    The labelling of blood cells in vitro for subsequent in vivo studies was one of the earliest applications of radioactive tracers in clinical medicine and laid the foundations for many important contributions to the advancement of knowledge of human blood cell pathophysiology. The characteristics required for satisfactory clinical studies, the mechanisms of cell labelling, the problems of radiation or chemical damage to the labelled cells and some examples of modern clinical applications are described and discussed. (Author)

  8. On labelled compounds nomenclature

    Different approaches of major labelled compounds producers to their nomenclature in technical and commercial documentation are discussed. Some draft options of a standard technical guide document for labelled compounds nomenclature rules are suggested. Such a document after due discussion by the experts will serve to unification of the labelled compounds nomenclature within the frame of the CMEA member-countries co-operation in this field. The suggested options are based on the general recommendations by the International Union of Pure and Applied Chemistry and incorporate some more accurate definitions originating from the labelled compounds production and application experience

  9. Photoreactivation of UV induced cell killing, chromosome aberrations, sister chromatide exchanges, mutations and pyrimidine dimers in Xenopus laevis fibroblasts

    Fibroblasts from Xenopus laevis, which posses photoreactivating enzyme were used to study the influence of photoreactivating light on the frequency of pyrimidine dimers in DNA, chromosomal aberrations, sister chromatid exchanges, cell killing and the induction of gene mutations (ouabain-resistance) induced by 254 nm ultraviolet irradiation. The frequency of all biological endpoints studied were reduced following exposure to photoreactivating light parallel to the reduction in the frequencies of pyrimidine dimers (determined as endonuclease sensitive sites). However, there was not always an absolute quantitative relationship between the reduction in the frequency of pyrimidine dimers and the reduction in the biological effects. This probably reflects a fast fixation process for the biological effects prior to removal of the dimers by photoreactivation. (orig.)

  10. The rate of removal of sunlight-induced pyrimidine dimers from the DNA of cultured human diploid fibroblasts

    The rate of excision of sunlight-induced pyrimidine dimers in DNA of exposed human cells was determined. Two normal excision repair-proficient human diploid fibroblast strains (WS-1 and KD) and a repair-deficient strain (XP12BE, group A) maintained in a nondividing state were exposed to summer noon-time sunlight for times (5 and 20 min) that induced numbers of dimers equivalent to far UV (254 nm) exposures of 1 and 4 J/m2. Pyrimidine dimers were quantified in extracted DNA using a UV-endonuclease-alkaline sedimentation assay. The excision rates of these dimers were similar to those observed for the excision of UV-induced pyrimidine dimers. No sunlight-induced inhibition or stimulation of DNA repair was observed in either strain at these low exposures. (author)

  11. Synthesis, in Vivo Anti-inflammatory, and in Vitro Antimicrobial Activity of New 5-Benzofuranyl Fused Pyrimidines.

    Nassar, Ekhlass; El-Badry, Yaser Abdel-Moemen; El Kazaz, Hagar

    2016-01-01

    Chalcone (3) has been synthesized as a new chalcone derivative bearing benzofuran moiety at 1 position. Such chalcone was used as a model dielectrophile applied to react with some nucleophiles such as 5-amino pyrazoles, 5-amino-1,2,4-triazole, 2-aminobenzimidazole, and 6-uraciles under Michael reaction conditions and resulted in a new series of fused pyrimidines such as pyrazolo[1,5-a]pyrimidines 7a-e, [1,2,4]-triazolo[1,5-a]pyrimidine 9, pyrimido[1,2-a]benzimidazole 11, and synthesis of pyrido[2,3-d]pyrimidinones 13a and b. The structures of the synthesized target heterocyclic compounds were confirmed by microanalytical and spectral data such as Fourier transform (FT)-IR, (1)H-NMR, and MS spectra. The newly synthesized compounds were evaluated for their anti-inflammatory and antimicrobial activities; most showed significant activities. PMID:27250790

  12. Consortium analysis of gene and gene–folate interactions in purine and pyrimidine metabolism pathways with ovarian carcinoma risk

    Kelemen, Linda E; Terry, Kathryn L; Goodman, Marc T;

    2014-01-01

    SCOPE: We reevaluated previously reported associations between variants in pathways of one-carbon (1-C) (folate) transfer genes and ovarian carcinoma (OC) risk, and in related pathways of purine and pyrimidine metabolism, and assessed interactions with folate intake. METHODS AND RESULTS: Odds......11587873 (OR = 0.92; p = 6 × 10(-5)) and rs828054 (OR = 1.06; p = 1 × 10(-4)). Thirteen variants in the pyrimidine metabolism genes, DPYD, DPYS, PPAT, and TYMS, also interacted significantly with folate in a multivariant analysis (corrected p = 9.9 × 10(-6)) but collectively explained only 0.2% of OC risk....... Although no other associations were significant after multiple testing correction, variants in SHMT1 in 1-C transfer, previously reported with OC, suggested lower risk at higher folate (p(interaction) = 0.03-0.006). CONCLUSION: Variation in pyrimidine metabolism genes, particularly DPYD, which...

  13. Synthesis of a New Series of Substituted Pyrimidines and Its Evaluation for Antibacterial and Antinociceptive Effects

    Waheed, Akhlaq; Alorainy, Mohammad S.; Alghasham, Abdullah A.; Khan, Suroor A.; Raza, Muhammad

    2008-01-01

    Background: Pyrimidines are a well known group of compounds reported to have different biological activities. Prompted from the diversity of its wider use and being an integral part of genetic material, an effort was made to synthesize a novel series of amino-pyrimidine derivatives of pharmaceutical interest by condensing the guanidinyl derivative of nalidixic acid with different chalcones. Methods: The structures of all synthesized compounds were established on the basis of IR and 1HNMR spectral studies. All of the new compounds in this series were screened for antimicrobial activity. Gram +ve and Gram −ve strains were used to ascertain the spectrum of activity. ED50 values in the tail flick test were determined and recorded. Analgesic potential of compounds by using tail flick test in SWR male mice have also revealed promising results. Results: All of the derivatives were effective in Gram –ve test against E. coli. None of the compounds show any inhibition of Gram +ve strain S. aureus. m-Bromo substitution derivative of amino-pyrimidines showed appreciable activity against E. coli, while 2,4 dichloro and p-chloro substitution derivatives also demonstrated improved activity. Compound 4 was most potent. The order of potency for these derivatives was 4>5≥6>1>2>7>3. Parallel to antimicrobial activity, m-bromo substitution derivative showed significant (P<0.01) antinociceptive response in comparison to control, and this effect was comparable to aspirin group. Trimethoxy substitution of benzene ring demonstrated moderate activity, whereas p-bromo substitution essentially had no antinociceptive effects in mice. Conclusion: Comparing meta- and para- bromo substitutions, there had been significant (P<0.01) difference in the antinociceptive response of both the bromo-substituted derivatives. It was observed that bromo-substitution at meta- position demonstrated comparatively higher potential for its antibacterial as well as antinociceptive properties. PMID:21475470

  14. Crystal structure of 4-allylsulfanyl-1H-pyrazolo[3,4-d]pyrimidine

    Mohammed El Fal

    2014-09-01

    Full Text Available In the title compound, C8H8N4S, the pyrazolo[3,4-d]pyrimidine ring system is essentially planar, with a maximum deviation from the mean plane of 0.025 (3 Å. The allyl group is disordered over two sites in a 0.512 (6:0.488 (6 ratio. In the crystal, molecules are linked by pairs of N—H...N hydrogen bonds, forming inversion dimers with an R22(8 graph-set motif.

  15. An Efficient method for Synthesis of Novel Iminothiazolo Pyrimidines and Plausible Antioxidant Potential

    Sambhaji P. Vartale

    2013-03-01

    Full Text Available 2-aminothiazole on treatment with bis(methylthiomethylene malononitrile in N, N'- dimethyl formamide (DMF and anhydrous potassium carbonate afforded 6-Cyano-5-imino-7- (methylthio-5H-thiazolo[3,2-a] pyrimidinewhich on further reacted with selected N–, O– and C– nucleophiles such as aryl and heteryl amines, substituted phenols and compounds with an active methylene group and synthesized 7-substituted derivatives of 6-Cyano-5-imino-5H-thiazolo [3,2- a] pyrimidine. These newly synthesized derivatives were further screened for their antioxidant potential.

  16. The effect of pK(a) on pyrimidine/pyridine-derived histamine H4 ligands.

    Savall, Brad M; Meduna, Steven P; Venable, Jennifer; Wei, Jianmei; Smith, Russell C; Hack, Michael D; Thurmond, Robin L; McGovern, Patricia; Edwards, James P

    2014-12-01

    During the course of our efforts toward the discovery of human histamine H4 antagonists from a series of 2-aminiopyrimidines, it was noted that a 6-trifluoromethyl group dramatically reduced affinity of the series toward the histamine H4 receptor. This observation was further investigated by synthesizing a series of ligands that varied in pKa of the pyrimidine derived H4 ligands by over five orders of magnitude and the effect on histamine H4 affinity. This trend was then extended to the discovery of C-linked piperidinyl-2-amino pyridines as histamine H4 receptor antagonists. PMID:25455490

  17. The use of pyr-mutations to modify pyrimidine pools in Lactococci

    Hansen, Steen Lyders Lerche; Martinussen, Jan; Hammer, Karin

    1999-01-01

    The specific engineering of organisms used for startercultures has become an effective way of improving and developing new products in the dairy industry. In order to obtain strains with specific characteristics, it is imperative to have a good understanding of the central biochemical pathways...... pyrimidines are only available through salvage of uracil and/or cytidine, the pools of CTP and UTP can be varied independently by controlling the activities of cytidine-deaminase (cdd) and CTP-synthetase (pyrG). Cytidine-deaminase catalyses the deamination of cytidine leading to uridine and CTP...

  18. The use of Pyr-mutants to modify pyrimidine metabolism in lactococci

    Hansen, Steen Lyders Lerche; Martinussen, Jan; Hammer, Karin

    1998-01-01

    The specific engineering of organisms used for startercultures has become an effective way of improving and developing new products in the dairy industry. In order to obtain strains with specific characteristics, it is imperative to have a good understanding of the central biochemical pathways...... pyrimidines are only available through salvage of uracil and/or cytidine, the pools of CTP and UTP can be varied independently by controlling the activities of cytidine-deaminase (cdd) and CTP-synthetase (pyrG). Cytidine-deaminase catalyses the deamination of cytidine leading to uridine and CTP...

  19. Structure-dependent NO-, PGE2- and cytokine-inhibitory effects of pyrimidine derivatives

    Zídek, Zdeněk; Kmoníčková, Eva; Janeba, Zlatko; Kolman, Viktor; Jansa, Petr

    organizátor symposia, 2014, s. 6-10. ISBN 978-80-971699-0-9. [Proceedings of the Joint Meeting of the 8th International Symposium Nitric Oxide: From Basic Regulations to Lifestyle-Related Diseases and The 2nd Genetic and Environmental Factors in Hypertension [0312302]. Vrsan (HR), 15.09.2014-19.09.2014] R&D Projects: GA ČR(CZ) GAP303/12/0172 Institutional support: RVO:68378041 ; RVO:61388963 Keywords : PGE2 * TNF-a * pyrimidine derivatives Subject RIV: FR - Pharmacology ; Medidal Chemistry

  20. Charge-transfer complexes of pyrimidine Schiff bases with aromatic nitro compounds

    Issa, Yousry M.; El Ansary, A. L.; Sherif, O. E.; Hassib, H. B.

    2011-08-01

    Charge-transfer (CT) complexes of pyrimidine Schiff bases, derived from condensation of 2-aminopyrimidine and substituted benzaldehydes, with some aromatic polynitro compounds were prepared and investigated using IR, UV, visible and 1H NMR spectroscopy. For all solid complexes, the main interaction between the donor and acceptor molecules takes place through the π-π* interaction. Strong and some weak acidic acceptors, in addition interact through proton transfer from the acceptor molecule to the basic centre of the electron donor. Also, an n-π* transition was detected in some complexes.

  1. DNA triple helix formation at oligopurine sites containing multiple contiguous pyrimidines.

    Gowers, D M; Fox, K R

    1997-01-01

    We have used DNase I footprinting to assess the formation of triple helices at 15mer oligopurine target sites which are interrupted by several (up to four) adjacent central pyrimidine residues. Third strand oligonucleotides were designed to generate complexes containing central (X.TA)nor (X.CG)n triplets (X = each base in turn) surrounded by C+.GC and T.AT triplets. It has previously been shown that G.TA and T.CG are the most stable triplets for recognition of single TA and CG interruptions. ...

  2. Action of purine and pyrimidine nucleotides on the rat superior cervical ganglion.

    Connolly, G. P.; P. J. Harrison; Stone, T.W.

    1993-01-01

    1. Using a grease-gap technique, we have investigated the effects of purine and pyrimidine nucleotides on the d.c. potential of the rat isolated superior cervical ganglion (SCG). 2. Of the purines tested, adenosine, adenosine 5'-triphosphate (ATP), beta,gamma-methylene-adenosine 5'-triphosphate (beta,gamma-MeATP) at up to 300 microM produced concentration-dependent hyperpolarizations, whereas 2-methyl-thio-ATP (2-Me.S.ATP) and alpha,beta-methylene-ATP (alpha,beta-MeATP) depolarized ganglia. O...

  3. Tetraaqua(pyrimidine-4,6-dicarboxylato-κ2N1,O6magnesium monohydrate

    Wojciech Starosta

    2013-04-01

    Full Text Available In the title compound, [Mg(C6H2N2O4(H2O4]·H2O, the MgII ion is coordinated by a fully deprotonated pyrimidine-4,6-dicarboxylate molecule, via a ring N and a carboxylate O atom, and by four water O atoms at the apices of a slightly distorted octahedron. In the crystal, molecules are linked by O—H...O and O—H...N hydrogen bonds, forming a three-dimensional network.

  4. Tandem Aldol-Michael Reactions in Aqueous Diethylamine Medium: A Greener and Efficient Approach to Bis-Pyrimidine Derivatives

    Abdullah M. Al-Majid

    2013-12-01

    Full Text Available A simple protocol, involving the green synthesis for the construction of novel bis-pyrimidine derivatives, 3a–i and 4a–e are accomplished by the aqueous diethylamine media promoted tandem Aldol-Michael reaction between two molecules of barbituric acid derivatives 1a,b with various aldehydes. This efficient synthetic protocol using an economic and environmentally friendly reaction media with versatility and shorter reaction time provides bis-pyrimidine derivatives with high yields (88%–99%.

  5. Mitotic arrest of breast cancer MDA-MB-231 cells by a halogenated thieno[3,2-d]pyrimidine

    Ross, Christina R.; Temburnikar, Kartik W; Wilson, Gerald M.; Seley-Radtke, Katherine L.

    2015-01-01

    Halogenated thieno[3,2-d]pyrimidines exhibit antiproliferative activity against a variety of cancer cell models, such as the mouse lymphocytic leukemia cell line L1210 in which they induce apoptosis independent of cell cycle arrest. Here we assessed these activities on MDA-MB-231 cells, a well-established model of aggressive, metastatic breast cancer. While 2,4-dichloro[3,2-d]pyrimidine was less toxic to MDA-MB-231 cells than previously observed in the L1210 model, flow cytometry analysis sho...

  6. Comparison of the cleavage of pyrimidine dimers by the bacteriophage T4 and Micrococcus luteus uv-specific endonucleases

    A comparison was made of the activity of the uv-specific endonucleases of bacteriophage T4 (T4 endonuclease V) and of Micrococcus luteus on ultraviolet light-irradiated DNA substrates of defined sequence. The two enzyms cleave DNA at the site of pyrimidine dimers with the same frequency. The products of the cleavage reaction are the same. The pyrimidine dimer DNA-glycosylase activity of both enzymes is more active on double-stranded DNA than it is on single-stranded DNA

  7. Stable isotopes labelled compounds

    The catalogue on stable isotopes labelled compounds offers deuterium, nitrogen-15, and multiply labelled compounds. It includes: (1) conditions of sale and delivery, (2) the application of stable isotopes, (3) technical information, (4) product specifications, and (5) the complete delivery programme

  8. Labeling and Delinquency.

    Adams, Mike S.; Robertson, Craig T.; Gray-Ray, Phyllis; Ray, Melvin C.

    2003-01-01

    Index comprised of six contrasting descriptive adjectives was used to measure incarcerated youths' perceived negative labeling from the perspective of parents, teachers, and peers. Results provided partial support for hypothesis that juveniles who choose a greater number of negative labels will report more frequent delinquent involvement. Labeling…

  9. Photoreversal-dependent release of thymidine and thymidine monophosphate from pyrimidine dimer-containing DNA excision fragments isolated from ultraviolet-damaged human fibroblasts

    To elucidate the enzymatic excision-repair process operative on cyclobutane-type pyrimidine photodimers in human dermal fibroblasts, we have examined excised dimer-containing material recovered in the trichloroacetic acid soluble fraction from far-ultraviolet-irradiated (254 nm, 40 J m-2) and incubated (24 h) cell cultures. The excised DNA photoproducts were found in oligonucleotide fragments with an estimated mean chain length of approximately 3.7 bases. Exposure of these isolated excision fragments, labeled with [3H]thymidine (dT), to a secondary, dimer-photoreversing fluence of far-UV (5.5 kJ m-2) resulted in the release of free dT and thymidine monophosphate (TMP). Photorelease of these two radioactive species was measured by high-performance liquid chromatography, with TMP being detected as the increase in dT following bacterial alkaline phosphatase treatment. These data imply that the photoliberated dT and TMP moieties were attached to the excision fragments solely by the cyclobutane ring of the dimer. No evidence was obtained for the photoliberation of free thymine, thus corroborating a conclusion reached by others that the excision of dimers in human cells is not initiated by scission of an intradimer N-glycosyl bond. The sum of the tritium label recovered in dT plus TMP corresponded to approximately 40% of that disappearing from thymine-containing dimers on photoreversal, suggesting that in about 80% of the isolated excision fragments the dimer is located at one end of the oligonucleotide and contains a break in its internal phosphodiester bond

  10. Label Fusion Strategy Selection

    Nicolas Robitaille

    2012-01-01

    Full Text Available Label fusion is used in medical image segmentation to combine several different labels of the same entity into a single discrete label, potentially more accurate, with respect to the exact, sought segmentation, than the best input element. Using simulated data, we compared three existing label fusion techniques—STAPLE, Voting, and Shape-Based Averaging (SBA—and observed that none could be considered superior depending on the dissimilarity between the input elements. We thus developed an empirical, hybrid technique called SVS, which selects the most appropriate technique to apply based on this dissimilarity. We evaluated the label fusion strategies on two- and three-dimensional simulated data and showed that SVS is superior to any of the three existing methods examined. On real data, we used SVS to perform fusions of 10 segmentations of the hippocampus and amygdala in 78 subjects from the ICBM dataset. SVS selected SBA in almost all cases, which was the most appropriate method overall.

  11. OR Specimen Labeling.

    Zervakis Brent, Mary Ann

    2016-02-01

    Mislabeled surgical specimens jeopardize patient safety and quality care. The purpose of this project was to determine whether labeling surgical specimens with two patient identifiers would result in an 80% reduction in specimen labeling errors within six months and a 100% reduction in errors within 12 months. Our failure mode effects analysis found that the lack of two patient identifiers per label was the most unsafe step in our specimen handling process. We piloted and implemented a new process in the OR using the Plan-Do-Check-Act conceptual framework. The audit process included collecting data and making direct observations to determine the sustainability of the process change; however, the leadership team halted the direct observation audit after four months. The total number of surgical specimen labeling errors was reduced by only 60% within six months and 62% within 12 months; therefore, the goal of the project was not met. However, OR specimen labeling errors were reduced. PMID:26849982

  12. Radioiodine and its labelled compounds

    Chemical characteristics and their nuclear characteristics, types of labelled molecules,labelling procedures, direct labelling with various oxidizing agents, indirect labelling with various conjugates attached to protein molecules, purification and quality control. Iodination damage.Safe handling of labelling procedures with iodine radioisotopes.Bibliography

  13. Chiral 6-aryl-furo[2,3-d]pyrimidin-4-amines as EGFR inhibitors.

    Han, Jin; Kaspersen, Svein Jacob; Nervik, Sondre; Nørsett, Kristin G; Sundby, Eirik; Hoff, Bård Helge

    2016-08-25

    Epidermal growth factor receptor inhibitors are of importance in cancer therapy and possibly in the management of pain. Herein, we report a structure-activity relationship study with 29 new 6-aryl-furo[2,3-d]pyrimidin-4-amines, involving modification of the 4-amino group and 6-aryl function. The EGFR activity was especially dependent on having a chiral 4-benzylamino group with correct stereochemistry. Molecular dynamics indicate this to be due to favourable cation-π interactions. The most active inhibitor identified, equipotent to Erlotinib, was substituted with (R)-1-phenylethylamine at C-4 and a N(1), N(1)-dimethyl-1,2-diamine group in para position of the 6-aryl moiety. These new furopyrimidines had a different off-target kinase profile when compared to Erlotinib, and also possessed high activity towards Ba/F3 EGFR(L858R) reporter cells. Further, comparing the EGFR data of the furo[2,3-d]pyrimidin-4-amines with that of the corresponding thieno- and pyrrolopyrimidines concludes the furopyrimidine scaffold to be highly useful for development of new epidermal growth factor receptor antagonists. PMID:27235841

  14. [Stimulation of the antiviral innate immune response by pyrimidine biosynthesis inhibitors: a surprise of phenotypic screening].

    Vidalain, Pierre-Olivier; Lucas-Hourani, Marianne; Helynck, Olivier; Tangy, Frédéric; Munier-Lehmann, Hélène

    2015-01-01

    RNA viruses are responsible for major human diseases such as flu, bronchitis, dengue, hepatitis C or measles. They also represent an emerging threat because of increased worldwide exchanges and human populations penetrating more and more natural ecosystems. Recent progresses in our understanding of cellular pathways controlling viral replication suggest that compounds targeting host cell functions, rather than the virus itself, could inhibit a large panel of RNA viruses. In particular, several academic laboratories and private companies are now seeking molecules that stimulate the host innate antiviral response. One appealing strategy is to identify molecules that induce the large cluster of antiviral genes known as Interferon-Stimulated Genes (ISGs). To reach this goal, we have developed a phenotypic assay based on human cells transfected with a luciferase reporter gene under control of an interferon-stimulated response element (ISRE). This system was used in a high-throughput screening of chemical libraries comprising around 54,000 compounds. Among validated hits, compound DD264 was shown to boost the innate immune response in cell cultures, and displayed a broad-spectrum antiviral activity. While deciphering its mode of action, DD264 was found to target the fourth enzyme of de novo pyrimidine biosynthesis, namely the dihydroorotate dehydrogenase (DHODH). Thus, our data unraveled a yet unsuspected link between pyrimidine biosynthesis and the innate antiviral response. PMID:25658737

  15. Pyrimidine-fused heterocycle derivatives as a novel class of inhibitors for α-glucosidase.

    Yousefi, Reza; Alavian-Mehr, Mohammad-Mehdi; Mokhtari, Fatemeh; Panahi, Farhad; Mehraban, Mohammad H; Khalafi-Nezhad, Ali

    2013-12-01

    The needs for diverse inhibitors of α-glucosidase (α-Gls) encouraged us to synthesize five different poly-hydroxy functionalized pyrimidine-fused heterocyclic (PHPFH) molecules, having either aliphatic or aromatic side chains (C1-C5) and their inhibitory activities were examined spectroscopically against yeast and mouse intestinal α-Gls. The results revealed that aromatic substitution of the synthetic compounds has significant impact on their inhibitory properties. Moreover C3 with the substituted moiety as 4-(4-aminophenylsulfonyl) phenyl (4-APSP) revealed strong inhibitory activity with non-competitive and competitive inhibition modes against yeast and mouse α-Gls, respectively. Furthermore, in the presence of increasing concentration of C3, both Trp and 1-anilinonaphthalene-8-sulfonic acid (ANS) fluorescence intensities of yeast α-Gls were gradually decreased, suggesting that C3 binding induced significant structural alteration which was accompanied with the reduction of hydrophobic surfaces. Also, the interaction between yeast α-Gls and C3 was proved to be spontaneous and driven mainly by hydrophobic forces. Overall, this study suggests that aromatic substitution on pyrimidine-fused heterocyclic (PFH) scaffold may represent a novel class of promising inhibitors of α-Gls. PMID:23043430

  16. Stabilities and Spectroscopy of Hydrogen Bonding Complexes Formed by 2,4-Bis(acrylamido)pyrimidines

    ZHANG Ye; LI Ting; TENG Qi-Wen

    2008-01-01

    Hydrogen bonds play important roles to living organisms containing pyrimidine-based derivatives.The electronic structures of the hydrogen bonding complexes formed by 2,4-bis(acrylamido)pyrimidine (2,4-BAAP) derivatives with 1-substituted uracil were studied using Austin Model 1 (AMl) and density function theory (DFT) methods.The UV and NMR spectra of the complexes were calculated with the INDO/CIS (configuration interaction for singlet in intermediate neglect of differential overlap) and B3LYP/6-31G(d)methods.It was shown that the complexes could be formed via the triple hydrogen bonding between two monomers owing to the negative binding energies.The binding energies of the complexes were weakened in the presence of substituents,but this weakening effect depended on the simultaneous influence of the electronic and steric effects.The binding energies of the complexes were also decreased owing to the formation of the isomeric complexes in the presence of piperidyl on 2,4-BAAP.The energy gaps of the complexes were lessened in the presence of electron-donating groups.Holes and electrons were easily injected to the complexes due to the extension of the conjugation chain.The first UV absorptions of the complexes relative to those of the parent compound were red-shifted because of the narrow energy gaps.The chemical shifts of the carbon atoms on the C=O bonds in the complexes were changed downfield.

  17. Quantitation of pyrimidine dimers in DNA from UVB-irradiated alfalfa (Medicago sativa L.) seedlings

    Depletion of stratospheric ozone will increase the solar ultraviolet radiation in the range from 290-320 nm (UVB) that reaches the surface of the earth, placing an increased UV burden on exposed organisms. One consequence of increased UVB may be decreased productivity of crop plants. A principal lesion caused by UV in DNA is the cyclobutyl pyrimidine dimer. We have adapted a method for measuring these dimers in nanogram quantities of non-radioactive DNA for use in UV-irradiated plants. We find that biologically relevant doses of broad band UVB radiation induce easily detectable frequencies of pyrimidine dimers in the DNA of irradiated alfalfa sprout leaves and that the dose response for dimer formation is linear up to doses of at least 690 J/m2. We also find easily measurable frequencies of dimers in the leaves of seedlings grown in glass filtered sunlight but not exposed to additional UVB, suggesting that significant number of dimers are formed in plants exposed to normal sunlight. 27 refs., 3 figs., 1 tab

  18. Formation of Nucleobases from the UV Photo-Irradiation of Pyrimidine in Astrophysical Ice Analogs

    Milam, S. N.; Nuevo, M.; Sandford, S. A.; Elsila, J. E.; Dworkin, J. P.

    2010-01-01

    Astrochemistry laboratory simulations have shown that complex organic molecules including compounds of astrobiological interest can be formed under interstellarl/circumstellar conditions from the vacuum UV irradiation of astrophysical ice analogs containing H2O, CO, CO2, CH3OH, NH13, etc. Of all prebiotic compounds, the formation of amino acids under such experimental conditions has been the most extensively studied. Although the presence of amino acids in the interstellar medium (ISM) has yet to be confirmed, they have been detected in meteorites, indicating that biomolecules and/or their precursors can be formed under extraterrestrial, abiotic conditions. Nucleobases, the building blocks of DNA and RNA, as well as other 1V-heterocycles, have also been detected in meteorites, but like amino acids, they have yet to be observed in the ISM. In this work, we present an experimental study of the formation of pyrimidine-based compounds from the UV photo-irradiation of pyrimidine in ice mixtures containing H2O, NH3, and/or CH3OH at low temperature and pressure.

  19. Synthesis and biological evaluation of new pyrazolo[3,4-d]pyrimidine derivatives

    Asma Agrebi

    2014-05-01

    Full Text Available Several new pyrazolopyrimidine compounds were achieved from aminocyanopyarazole 1. The starting material 1 was initially coupled with orthoester at refluxed with various primary amines, ammonia, hydrazines and hydroxylamine to furnish a series of pyrazolo[3,4-d]pyrimidines. The reaction of imidate 2a-b with hydrazide derivatives led to the formation of pyrazolo[3,4-d][1,2,4]triazolo[4,3-c]pyrimidines. Some of the synthesized compounds 3a and 4c were evaluated for their anti-inflammatory, antipyretic and nociceptive activities. We start by studing the toxicity of these two molecules by measuring the corresponding DL50. The DL50 of 3a and 4c are estimated to 1333.2mg / kg and 1593.5mg / kg respectively. Pharmacological evaluation showed that compounds 3a and 4c at doses (5.5-22.2 mg / Kg, i.p exhibited anti-inflammatory activities compared to Ibuprofen (150 mg / Kg, i.p, used as a refer ence drug. Further, our study showed that the injection of derived pyrazolopyrimidines on hyperthermic animal leads to a decrease in temperature after 1 hours of treatment compared to paracetamol used as reference. In addition, the injection of derived pyrazolopyrimidines at different doses contains a potent nociceptive activity. This effect is dose-dependent compared to aspirin.

  20. New Routes to Pyridino[2,3-d]pyrimidin-4-one and Pyridino-[2,3-d]triazolino[4,5-a]pyrimidin-5-one Derivatives

    Tayseer A. Abdallah

    2003-03-01

    Full Text Available 2-Thioxopyrimidinyl-5-(N,N-dimethylaminoformamidine (5 and 1,3-diphenyltriazolo[3,4-d]pyrimidinyl-N,N-dimethylformamidine (14 were prepared by condensation of 6-amino-2-thioxo-1,3-dihydropyrimidin-4-one (2 and 7-amino-1,3-diphenyl-1,2,4-triazolo[4,3-a]pyrimidin-4-one (13 with dimethylformamide dimethyl-acetal (DMFDMA. Compound 5 reacts with acetophenone and 2-acetylthiophene to give the 2-thioxo-1,3-dihydropyridino[2,3-d]pyrimidin-4-ones 3a and 3b, respectively. Compounds 3a,b react with hydrazonoyl halides 6,7 to give pyridino[2,3-d]triazolo[4,5-a]pyrimidin-4-ones 11a-d and not the isomeric structures 12a-d. Formamidines of type 14 react with ethyl cyanoacetate, malononitrile and benzoyl acetonitrile to give the 1,3-diphenyl-3a-hydropyridino[2,3-d]1,2,4-triazolo[4,5-a]pyrimidin-4-one derivatives 15a,b and 18, respectively. The structures of the newly synthesized compounds are established on the basis of chemical and spectroscopic evidences as well as their synthesis by alternative methods.

  1. Nutrition Facts: Reading the Label

    ... My Go4Life Get Free Stuff Be a Partner Nutrition Facts: Reading the Label Reading labels can help ... of information on their labels or packaging about nutrition and food safety. Product dates . You might see ...

  2. Radioactive labelled orgotein

    The preparation and use of radioactively labelled orgotein, i.e. water-soluble protein congeners in pure, injectable form, is described. This radiopharmaceutical is useful in scintigraphy, especially for visualization of the kidneys where the orgotein is rapidly concentrated. Details of the processes for labelling bovine orgotein with sup(99m)Tc, 60Co, 125I or 131I are specified. The pharmaceutical preparation of the labelled orgotein for intravenous and parenteral administration is also described. Examples using either sup(99m)TC or 125I-orgotein in scintiscanning dogs' kidneys are given. (UK)

  3. Clinical applications of cells labelling

    Blood cells labelled with radionuclides are reviewed and main applications are described. Red blood cell labelling by both random and specific principle. A table with most important clinical uses, 99mTc labelling of RBC are described pre tinning and in vivo reduction of Tc, in vitro labelling and administration of labelled RBC and in vivo modified technique. Labelled leucocytes with several 99mTc-complex radiopharmaceuticals by in vitro technique and specific monoclonal s for white cells(neutrofiles). Labelled platelets for clinical use and research by in vitro technique and in vivo labelling

  4. Novel phenyl(2-(phenylamino)pyrimidin-4-yl)methanones as potent non-nucleoside reverse transcriptase inhibitors

    Šimon, Petr; Baszczyňski, Ondřej; Šaman, David; Bahador, G.; Stepan, G.; Hu, E.; Lansdon, E.; Jansa, P.; Janeba, Zlatko

    Rome: International Society for Antiviral Research (ISAR), 2015. s. 96. [International Conference on Antiviral Research /28./. 11.05.2015-15.05.2015, Rome] Institutional support: RVO:61388963 Keywords : non-nucleoside reverse transcriptase inhibitors * pyrimidine * HIV -1 Subject RIV: CC - Organic Chemistry

  5. Synthesis of some pyrazolo[3,4-d]pyrimidines and their fused triazole and tetrazole derivatives

    MAGDI E. A. ZAKI

    1999-11-01

    Full Text Available Reaction of 2 with different reagents, namely formic acid, acetic anhydride and trichloroacetonitrile, yielded pyrazolo[3,4-d]pyrimidine derivatives 3, 5 and 6, respectively. Pyrazolo[3,4-d]pyrimidine m-thiazine(7 and 2,4-(1H,3Hdithione (8 derivatives were formed by the action of carbon disulfide on 2, depending on the reaction medium. Interaction of 7 with hydrazine hydrate yielded the aminoimino derivative 9 which reacted with acetic anhydride, triethyl orthoacetate and/or appropriate aldehydes to give 11, 12 and 13a,b, respectively. Methylation of compound 8 gave 14, which reacted with hydrazine hydrate to afford the monohydrazino derivative 15. Reaction of 15, with formic acid and nitrous acid afforded pyrazolo[4,3-e]triazolo[1,5-c]pyrimidine (16 and pyrazolo[4,3-e]tetrazolo-[1,5-c]pyrimidine (17 derivatives, respectively. The structures of products 3-17 were identified in light of their elemental analyses and spectra data.

  6. Synthesis and structure-activity relationship studies of polysubstituted pyrimidines as inhibitors of immune-activated nitric oxide production

    Jansa, Petr; Holý, Antonín; Dračínský, Martin; Kolman, Viktor; Janeba, Zlatko; Kmoníčková, Eva; Zídek, Zdeněk

    2015-01-01

    Roč. 24, č. 5 (2015), s. 2154-2166. ISSN 1054-2523 R&D Projects: GA ČR(CZ) GAP303/12/0172; GA MV VG20102015046 Institutional support: RVO:61388963 ; RVO:68378041 Keywords : pyrimidine * nitric oxide * NO * anti-inflammatory Subject RIV: CC - Organic Chemistry Impact factor: 1.402, year: 2014

  7. The role of pyrimidine and water as underlying molecular constituents for describing radiation damage in living tissue: A comparative study

    Water is often used as the medium for characterizing the effects of radiation on living tissue. However, in this study, charged-particle track simulations are employed to quantify the induced physicochemical and potential biological implications when a primary ionising particle with energy 10 keV strikes a medium made up entirely of water or pyrimidine. Note that pyrimidine was chosen as the DNA/RNA bases cytosine, thymine, and uracil can be considered pyrimidine derivatives. This study aims to assess the influence of the choice of medium on the charged-particle transport, and identify how appropriate it is to use water as the default medium to describe the effects of ionising radiation on living tissue. Based on the respective electron interaction cross sections, we provide a model, which allows the study of radiation effects not only in terms of energy deposition (absorbed dose and stopping power) but also in terms of the number of induced molecular processes. Results of these parameters for water and pyrimidine are presented and compared

  8. Ultraviolet-endonuclease activity in cell extracts of Saccharomyces cerevisiae mutants defective in excision of pyrimidine dimers

    Cell-free extracts of ultraviolet-sensitive mutants of Saccharomyces cerevisiae defective in excision of pyrimidine dimers, rad1, rad2, rad3, rad4, rad10, and rad16, as well as the extracts of the wild-type strain RAD+, display ultraviolet-endonuclease activity

  9. Chemistry of isoflavone heterocyclic analogs. 10. Synthesis of pyrimidines by recyclization of isoflavones and their heterocyclic analogs

    Khilya, V.P.; Kornilov, M.Yu.; Gorbulenko, N.V.; Golubushina, G.M.; Kovtun, E.N.; Kolotusha, N.V.; Panasenko, G.V.

    1986-05-01

    Isoflavones and their thiazole and pyrazole analogs are recyclized into the corresponding 4-(2-hydroxyphenyl)-pyrimidine derivatives under the effect of amidines. Their PMR spectra were studied. The effects related to the formation and strength of the intramolecular hydrogen bond were examined.

  10. Pyrimidine dimers are not the principal pre-mutagenic lesions induced in lambda phage DNA by ultraviolet light

    Experiments were performed to examine the role of cyclobutyl pyrimidine dimers in the process of mutagenesis by ultraviolet light. Lambda phage DNA was irradiated with u.v. and then incubated with an Escherichia coli photoreactivating enzyme, which monomerizes cyclobutyl pyrimidine dimers upon exposure to visible light. The photoreactivated DNA was packaged into lambda phage particles, which were used to infect E. coli uvr- host cells that had been induced for SOS functions by ultraviolet irradiation. Photoreactivation removed most toxic lesions from irradiated phage, but did not change the frequency of induction of mutations to the clear-plaque phenotype. This implies that cyclobutyl pyrimidine dimers can be lethal, but usually do not serve as sites of mutations in the phage. The DNA sequences of mutants, derived from photoreactivated DNA showed that almost two-thirds (16/28) were transitions, the same fraction found for u.v. mutagenesis without photoreactivation. Thus the lesion inducing transitions is not the cyclobutyl pyrimidine dimer. Photoreactivation of SOS-induced host cells before infection with u.v.-irradiated phage reduced mutagenesis substantially. In this case, photoreversal of cyclobutyl dimers serves to reduce expression of the SOS functions that are required in targeted u.v. mutagenesis. (author)

  11. The role of pyrimidine and water as underlying molecular constituents for describing radiation damage in living tissue: A comparative study

    Fuss, M. C.; Ellis-Gibbings, L. [Instituto de Física Fundamental, Consejo Superior de Investigaciones Científicas (CSIC), Serrano 113-bis, 28006 Madrid (Spain); Jones, D. B. [School of Chemical and Physical Sciences, Flinders University, GPO Box 2100, Adelaide, South Australia 5001 (Australia); Brunger, M. J. [School of Chemical and Physical Sciences, Flinders University, GPO Box 2100, Adelaide, South Australia 5001 (Australia); Institute of Mathematical Sciences, University of Malaya, 50603 Kuala Lumpur (Malaysia); Blanco, F. [Departamento de Física Atómica, Molecular y Nuclear, Universidad Complutense de Madrid, Avenida Complutense, 28040 Madrid (Spain); Muñoz, A. [Centro de Investigaciones Energéticas Medioambientales y Tecnológicas, Avenida Complutense 22, 28040 Madrid (Spain); Limão-Vieira, P. [School of Chemical and Physical Sciences, Flinders University, GPO Box 2100, Adelaide, South Australia 5001 (Australia); Laboratório de Colisões Atómicas e Moleculares, CEFITEC, Departamento de Física, Faculdade de Ciências e Tecnologia, Universidade Nova de Lisboa, 2829-516 Caparica (Portugal); García, G., E-mail: g.garcia@csic.es [Instituto de Física Fundamental, Consejo Superior de Investigaciones Científicas (CSIC), Serrano 113-bis, 28006 Madrid (Spain); Centre for Medical Radiation Physics, University of Wollongong, Wollongong, NSW 2522 (Australia)

    2015-06-07

    Water is often used as the medium for characterizing the effects of radiation on living tissue. However, in this study, charged-particle track simulations are employed to quantify the induced physicochemical and potential biological implications when a primary ionising particle with energy 10 keV strikes a medium made up entirely of water or pyrimidine. Note that pyrimidine was chosen as the DNA/RNA bases cytosine, thymine, and uracil can be considered pyrimidine derivatives. This study aims to assess the influence of the choice of medium on the charged-particle transport, and identify how appropriate it is to use water as the default medium to describe the effects of ionising radiation on living tissue. Based on the respective electron interaction cross sections, we provide a model, which allows the study of radiation effects not only in terms of energy deposition (absorbed dose and stopping power) but also in terms of the number of induced molecular processes. Results of these parameters for water and pyrimidine are presented and compared.

  12. Perturbation of maintenance and de novo DNA methylation in vitro by UVB (280-340 nm)-induced pyrimidine photodimers

    The effect of pyrimidine photodimers on transmethylation reactions catalyzed by a highly purified rat liver DNA (cytosine-5-)-methyltransferase (EC 2.1.1.37) that exhibits maintenance and de novo methylation activities was studied in vitro, using the viral substrates M13 mp9 replicative form (RF) DNA and the hemimethylated analog formed from primed synthesis of phage DNA in the presence of 2'-deoxy-5-methylcytidine 5'-triphosphate. These DNAs were irradiated with UVB (280-340 nm) at 900-3600 J/m2 in the presence of the triplet-state sensitizers acetone or 3-dimethylaminopropiophenone. Under these conditions of irradiation, which approximate solar UV, pyrimidine cyclobutane photodimers were introduced without producing any evidence of single-strand breaks or alkali-sensitive sites. The methylation of irradiated templates by DNA methyltransferase was inhibited in an approximately linear fashion as a function of increasing UVB dose. This inhibition was correlated with the number of lethal photoproducts detected by the simultaneous measurement of the surviving fraction of infectious phage DNA. For approximately the same number of pyrimidine cyclobutane photoproducts introduced, de novo methylation activity was approx. =2-fold more sensitive than the maintenance mode of methylation. The ability of these putatively carcinogenic, pyrimidine photoproducts to inhibit DNA methylation suggests a common mechanism of action with several chemical carcinogens that are known to modify bases

  13. Synthesis and evaluation of thymidine kinase 1-targeting carboranyl pyrimidine nucleoside analogs for boron neutron capture therapy of cancer.

    Agarwal, Hitesh K; Khalil, Ahmed; Ishita, Keisuke; Yang, Weilian; Nakkula, Robin J; Wu, Lai-Chu; Ali, Tehane; Tiwari, Rohit; Byun, Youngjoo; Barth, Rolf F; Tjarks, Werner

    2015-07-15

    A library of sixteen 2nd generation amino- and amido-substituted carboranyl pyrimidine nucleoside analogs, designed as substrates and inhibitors of thymidine kinase 1 (TK1) for potential use in boron neutron capture therapy (BNCT) of cancer, was synthesized and evaluated in enzyme kinetic-, enzyme inhibition-, metabolomic-, and biodistribution studies. One of these 2nd generation carboranyl pyrimidine nucleoside analogs (YB18A [3]), having an amino group directly attached to a meta-carborane cage tethered via ethylene spacer to the 3-position of thymidine, was approximately 3-4 times superior as a substrate and inhibitor of hTK1 than N5-2OH (2), a 1st generation carboranyl pyrimidine nucleoside analog. Both 2 and 3 appeared to be 5'-monophosphorylated in TK1(+) RG2 cells, both in vitro and in vivo. Biodistribution studies in rats bearing intracerebral RG2 glioma resulted in selective tumor uptake of 3 with an intratumoral concentration that was approximately 4 times higher than that of 2. The obtained results significantly advance the understanding of the binding interactions between TK1 and carboranyl pyrimidine nucleoside analogs and will profoundly impact future design strategies for these agents. PMID:26087030

  14. The role of pyrimidine and water as underlying molecular constituents for describing radiation damage in living tissue: A comparative study

    Fuss, M. C.; Ellis-Gibbings, L.; Jones, D. B.; Brunger, M. J.; Blanco, F.; Muñoz, A.; Limão-Vieira, P.; García, G.

    2015-06-01

    Water is often used as the medium for characterizing the effects of radiation on living tissue. However, in this study, charged-particle track simulations are employed to quantify the induced physicochemical and potential biological implications when a primary ionising particle with energy 10 keV strikes a medium made up entirely of water or pyrimidine. Note that pyrimidine was chosen as the DNA/RNA bases cytosine, thymine, and uracil can be considered pyrimidine derivatives. This study aims to assess the influence of the choice of medium on the charged-particle transport, and identify how appropriate it is to use water as the default medium to describe the effects of ionising radiation on living tissue. Based on the respective electron interaction cross sections, we provide a model, which allows the study of radiation effects not only in terms of energy deposition (absorbed dose and stopping power) but also in terms of the number of induced molecular processes. Results of these parameters for water and pyrimidine are presented and compared.

  15. FDA Online Label Repository

    U.S. Department of Health & Human Services — The drug labels and other drug-specific information on this Web site represent the most recent drug listing information companies have submitted to the Food and...

  16. Like your labels?

    Field, Michele

    2010-01-01

    The descriptive “conventions” used on food labels are always evolving. Today, however, the changes are so complicated (partly driven by legislation requiring disclosures about environmental impacts, health issues, and geographical provenance) that these labels more often baffle buyers than enlighten them. In a light-handed manner, the article points to how sometimes reading label language can be like deciphering runes—and how if we are familiar with the technical terms, we can find a literal meaning, but still not see the implications. The article could be ten times longer because food labels vary according to cultures—but all food-exporting cultures now take advantage of our short attention-span when faced with these texts. The question is whether less is more—and if so, in this contest for our attention, what “contestant” is voted off. PMID:21539053

  17. Certified Rule Labeling

    Nagele, Julian; Zankl, Harald

    2015-01-01

    The rule labeling heuristic aims to establish confluence of (left-)linear term rewrite systems via decreasing diagrams. We present a formalization of a confluence criterion based on the interplay of relative termination and the rule labeling in the theorem prover Isabelle. Moreover, we report on the integration of this result into the certifier CeTA, facilitating the checking of confluence certificates based on decreasing diagrams for the first time. The power of the method is illustrated by ...

  18. Labelling of Vincamine derivatives

    Tritium labelled Vincamine and ethyl apovincaminate (Cavinton) have been prepared on the bases of known stereospecific synthesis. High specific activity compounds were obtained by the catalytic tritiation of appropriate unsaturated starting compounds. When the structure of the unsaturated starting compounds was changed (even rather for from the reaction centre) instead of the catalytic addition of tritium a specific hydrogen-tritium exchange reaction was found to be the main labelling process

  19. Labelling of electricity

    This comprehensive report for the Swiss Federal Office of Energy (SFOE) presents a possible course of action to be taken to provide a means of declaring the sources of electrical power, as is foreseen in the draft of new Swiss electricity market legislation. The report presents the basic ideas behind the idea and defines the terms used such as labelling, certificates and declarations. Also, the legal situation in the European Union and in Switzerland is examined and a quantitative overview of electricity production and consumption is presented. Suggestions for a labelling scheme are made and some of the problems to be expected are looked at. The report also presents a series of examples of labelling schemes already implemented in other countries, such as Austria, Great Britain, Sweden and Germany. Tradable certificates and tracking systems are discussed as are initial quality labels like the Swiss 'Naturemade' label for green power. A concrete recommendation for the declaration and labelling of electricity in Switzerland is presented and various factors to be considered such as import/export, pumped storage, distribution losses, small-scale producers as well as the time-scales for introduction are discussed

  20. Structural modifications leading to changes in supramolecular aggregation of thiazolo[3, 2-]pyrimidines: Insights into their conformational features

    H Nagarajaiah; Noor Shahina Begum

    2014-09-01

    The compounds, 7-methyl-3,5-diphenyl-5-thiazolo[3,2-a]pyrimidine-6-carboxylic acid ethyl ester (1), 3-amino-2-cyano-7-methyl-5-phenyl-5-thiazolo[3,2-]pyrimidine-6-carboxylic acid methyl ester (2), 2-dimethylaminomethylene-7-methyl-3-oxo-5-phenyl-2,3-dihydro-5-thiazolo[3,2-]pyrimidine-6-carboxylic acid ethyl ester (3), 2-(3-cyano-benzylidene)-5-(4-hydroxy-phenyl)-7-methyl-3-oxo-2,3-dihydro-5-thiazolo[3,2-]pyrimidine-6-carboxylic acid methyl ester; with ,-dimethyl-formamide (4) and 3-ethoxycarbonylmethyl-5-(4-hydroxy-3-methoxy-phenyl)-7-methyl-5-thiazolo[3,2-]pyrimidine-6-carboxylic acid methyl ester (5) have been synthesized and their structures evaluated crystallographically. Compound 1 crystallizes in the space group $\\bar{ı}$ with Z=8, with four molecules in the asymmetric unit. Compound 2 also crystallizes in the space group $\\bar{ı}$ with Z=4 wherein asymmetric unit accommodates two molecules. Compound 3 belongs to 21/ with Z=4, compound 4 crystallizes in bc21 with Z= 4 and compound 5 belongs to $\\bar{ı}$ with Z=2. In all the above compounds, the aryl ring positioned at C5 of thiazolopyrimidine ring is almost perpendicular. In the case of compounds with substituted phenyl ring, aryl group-up conformation predominates. However, for compounds with unsubstituted phenyl ring, aryl group-down conformation is adopted. By varying the substituents at positions C2, C3, C6 and on the aryl at C5 in the main molecular scaffold of (1-5), we have observed significant differences in the intermolecular interaction patterns. The packing features of the compounds are controlled by C-H…O, C-H…N, N-H…N O-H…N, C-H$\\ldots$ and $\\ldots$ weak interactions.

  1. Inhibition of cyclobutane pyrimidine dimer formation in epidermal p53 gene of UV-irradiated mice by alpha-tocopherol

    Mutations or alterations in the p53 gene have been observed in 50-100% of ultraviolet light (UV)-induced squamous cell carcinoma in humans and animals. Most of the mutations occurred at dipyrimidine sequences, suggesting that pyrimidine dimers in the p53 gene play a role in the pathogenesis of cutaneous squamous cell carcinoma. We previously showed that topical alpha-tocopherol prevents UV-induced skin carcinogenesis in the mouse. In the present study we asked whether topical alpha-tocopherol reduces the level of UV-induced cyclobutane pyrimidine dimers in the murine epidermal p53 gene. Mice received six dorsal applications of 25 mg each of alpha-tocopherol, on alternate days, before exposure to 500 J/m2 of UV-B irradiation. Mice were killed at selected times after irradiation. The level of dimers in the epidermal p53 gene was measured using the T4 endonuclease V assay with quantitative Southern hybridization. Topical alpha-tocopherol caused a 55% reduction in the formation of cyclobutane pyrimidine dimers in the epidermal p53 gene. The rate of reduction of pyrimidine dimers between 1 and 10 hours after irradiation was similar in UV-irradiated mice, regardless of alpha-tocopherol treatment. Therefore, the lower level of cyclobutane pyrimidine dimers in UV-irradiated mice treated with alpha-tocopherol than in control UV-irradiated mice resulted from the prevention of formation of the dimers, and not from enhanced repair of these lesions. Our results indicate that alpha-tocopherol acts as an effective sunscreen in vivo, preventing the formation of premutagenic DNA lesions in a gene known to be important in skin carcinogenesis

  2. Synthesis, characterization and RHF/ab initio simulations of 2-amino-1,3,4-thiadiazole and its annulated ring junction pyrimidine derivatives

    Wafaa S. Hamama

    2013-01-01

    Full Text Available Michael addition reaction of the 2-amino-1,3,4-thiadiazole to chalcone as biselectrophile afforded 5,7-diphenyl-6-[1,3-diphenylpropan-1-on-3-yl][1,3,4]thiadiazolo[3,2-a]pyrimidine (3 instead of 5,7-diphenyl-5H-[1,3,4]thiadiazolo[3,2-a]pyrimidine (5 via further Michael addition at C5 in pyrimidine moiety. The structure 3 was established through the aspect of ab initio calculations, elemental analysis and spectral data.

  3. Synthesis, characterization and RHF/ab initio simulations of 2-amino-1,3,4-thiadiazole and its annulated ring junction pyrimidine derivatives

    Wafaa S. Hamama; Gouda, Moustafa A.; Mamdouh S. Soliman; Badr, Marwa H.; Zoorob, Hanafi H.

    2013-01-01

    Michael addition reaction of the 2-amino-1,3,4-thiadiazole to chalcone as biselectrophile afforded 5,7-diphenyl-6-[1,3-diphenylpropan-1-on-3-yl][1,3,4]thiadiazolo[3,2-a]pyrimidine (3) instead of 5,7-diphenyl-5H-[1,3,4]thiadiazolo[3,2-a]pyrimidine (5) via further Michael addition at C5 in pyrimidine moiety. The structure 3 was established through the aspect of ab initio calculations, elemental analysis and spectral data.

  4. Synthesis and antimicrobial activity of some new 2-amino pyrimidine derivatives from 1-(3,5-dibromo-2-hydroxy-4 methyl phenyl ethanone

    Milind P.Pawar

    2012-06-01

    Full Text Available The newly synthesized pyrimidine derivatives exhibited moderate to good antimicrobial activity respectto standard drugs. In present investigation, we report the synthesis of 2-amino pyrimidine fromchalcones and guanidine hydrochloride using potassium tetr-butoxide as base. These synthesizedcompounds were characterized on the basis of IR, 1HNMR, Mass spectroscopic data. All synthesizednew 2-amino pyrimidine derivatives were screened for antibacterial and antifungal activity againstdifferent strains as compare to standard drugs Amoxicillin and Griseofulvin. Compound 3a, 3b, 3d, 3gand 3f were found to be active against selected antibacterial and antifungal strains.

  5. Streaming Label Learning for Modeling Labels on the Fly

    You, Shan; Xu, Chang; Wang, Yunhe; Xu, Chao; Tao, Dacheng

    2016-01-01

    It is challenging to handle a large volume of labels in multi-label learning. However, existing approaches explicitly or implicitly assume that all the labels in the learning process are given, which could be easily violated in changing environments. In this paper, we define and study streaming label learning (SLL), i.e., labels are arrived on the fly, to model newly arrived labels with the help of the knowledge learned from past labels. The core of SLL is to explore and exploit the relations...

  6. Eco-labelling, competition and environment: Endogenization of labelling criteria

    Ben Youssef, Adel; Lahmandi-Ayed, Rim

    2008-01-01

    This paper suggests a modelling of the labelling procedure consistent with empirical observations, that allows the endogenous calculation of labelling criteria. The authority in charge of the labelling program chooses the level of labelling criteria so as to maximise the social surplus, anticipating competition between firms in environmental qualities and prices. While accounting simply for the informational role of labels, this model allows to understand observed behavior such as firms' igno...

  7. On online labeling with polynomially many labels

    Babka, M.; Bulánek, Jan; Čunát, V.; Koucký, Michal; Saks, M.

    Berlin : Springer, 2012 - (Epstein, L.; Ferragina, P.), s. 121-132 ISBN 978-3-642-33089-6. - (Lecture Notes in Computer Science. 7501). [20th Annual European Symposium on Algorithms (ESA 2012). Ljubljana (SI), 10.09.2012-12.09.2012] R&D Projects: GA ČR GAP202/10/0854; GA AV ČR IAA100190902 Institutional support: RVO:67985840 Keywords : online labeling * file maintenance problem * lower bounds Subject RIV: BA - General Mathematics http://link.springer.com/chapter/10.1007/978-3-642-33090-2_12

  8. European consumers and nutrition labelling

    Wills, Josephine M.; Grunert, Klaus G.; Celemín, Laura Fernández;

    2009-01-01

    Nutrition labelling of food in Europe is not compulsory, unless a nutrition or health claim is made for the product. The European Commission is proposing mandatory nutrition labelling, even front of pack labelling with nutrition information. Yet, how widespread is nutrition labelling in the EU...

  9. Genetic algorithms for map labeling

    Dijk, Steven Ferdinand van

    2002-01-01

    Map labeling is the cartographic problem of placing the names of features (for example cities or rivers) on the map. A good labeling has no intersections between labels. Even basic versions of the problem are NP-hard. In addition, realistic map-labeling problems deal with many cartographic constr

  10. Off-Label Drug Use

    ... Your Local Offices Close + - Text Size Off-label Drug Use What is off-label drug use? In the United States new drugs are ... unapproved use of a drug. Is off-label drug use legal? The off-label use of FDA- ...

  11. Enhanced DNA repair of cyclobutane pyrimidine dimers changes the biological response to UV-B radiation

    Yarosh, Daniel B

    2002-11-30

    The goal of DNA repair enzyme therapy is the same as that for gene therapy: to rescue a defective proteome/genome by introducing a substitute protein/DNA. The danger of inadequate DNA repair is highlighted in the genetic disease xeroderma pigmentosum. These patients are hypersensitive to sunlight and develop multiple cutaneous neoplasms very early in life. The bacterial DNA repair enzyme T4 endonuclease V was shown over 25 years ago to be capable of reversing the defective repair in xeroderma pigmentosum cells. This enzyme, packaged in an engineered delivery vehicle, has been shown to traverse the stratum corneum, reach the nuclei of living cells of the skin, and enhance the repair of UV-induced cyclobutane pyrimidine dimers (CPD). In such a system, changes in DNA repair, mutagenesis, and cell signaling can be studied without manipulation of the genome.

  12. Photo- and radio-induced radical oxidation of the purine and pyrimidine bases of nucleic acids

    Our current knowledge of the hydroxyl radical-mediated oxidations of the base moiety of the four main DNA 2'-deoxyribonucleosides, in aerated aqueous solutions, is reviewed. Included are kinetic and mechanistic aspects of transient radicals and structural features of the diamagnetic decomposition products. Another major topic addressed in this survey involves the chemical reactions of the purine and pyrimidine radical cations of the above DNA model compounds. These radicals are the main reactive intermediates of the direct effect of ionizing radiation and photosensitized reactions involving type I processes. Emphasis is placed on the similarities between the formation of oxidizing radicals via hydroxyl radical addition to the base moieties and chemical reactions of the radical cations (hydration and/or deprotonation). A survey of the main base lesions which have been characterized within isolated and cellular DNAs under conditions of oxidative stress, including exposure to ionizing radiation and various radiomimetic agents, is also presented. 97 refs

  13. Synthesis of novel indolyl-pyrimidine antiinflammatory, antioxidant and antibacterial agents

    Panda S

    2008-01-01

    Full Text Available A number of chalcones were synthesized by reacting indole-3-aldehyde, prepared by Vilsemeir Haack reaction with 4-substituted acetophenone in NaOH solution in ethanol. These chalcones were immediately reacted with urea, thiourea and guanidine hydrochloride in presence of concentrated hydrochloric acid as reagent to obtain the corresponding hydroxy, thio and amino pyrimidines. The synthesized heterocyclics were characterized on the basis of physical, chemical tests and spectroscopic data and were tested for the acute antiinflammatory activity, antioxidant, antibacterial activity using carragenan-induced rat paw oedema method, DPPH (diphenylpicrylhydrazyl radical scavenging method and cup plate method using Muller-Hinton agar media respectively. Evaluation of the compounds revealed remarkable antiinflammatory activity reflected by their ability to reduce the carragenan-induced inflammation in rats, appreciable antioxidant activity and also antibacterial activity was observed.

  14. 4'-Substituted pyrimidine nucleosides lacking 5'-hydroxyl function as potential anti-HCV agents.

    Shakya, Neeraj; Vedi, Satish; Liang, Chao; Yang, Fang; Agrawal, Babita; Kumar, Rakesh

    2014-03-01

    Hepatitis C virus (HCV) infection is one of the major health problems worldwide. If left untreated, it leads to liver cirrhosis, liver cancer and death. Herein, we report synthesis and anti-HCV activity of a new class of pyrimidine nucleosides possessing a 4'-carboxymethyl (9-16, 21 and 23) or 4'-carboxamide function (17-19 and 24). Among these, 10-12 (EC50=33.1-42.4 μM), 14 and 21 (EC50=43.4-59.5 μM) exhibited potent activity in HCV-1a replicon cells without any toxicity to parent Huh-7 cells (CC50=>829-1055 μM). The anti-HCV activities demonstrated by this unusual class of compounds were superior to that of ribavirin (EC50=81.9 μM). Further, the most active analog, 12, was found to interact synergistically with ribavirin to inhibit HCV RNA replication. PMID:24485784

  15. Synthesis, characterization and antimicrobial screening of hybrid molecules containing quinoline, pyrimidine and morpholine analogues

    N C Desai; K M Rajpara; V V Joshi; H V Vaghani; H M Satodiya

    2013-03-01

    In an attempt to find new bio-active molecules, a series of compounds -(4-(2-chloroquinolin-3-yl)-6-(aryl)pyrimidin-2-yl)-2-morpholinoacetamides (5a-l) were synthesized by multistep reactions. Compounds were characterized by IR, NMR and mass spectra. Antimicrobial screening of title compounds (5a-l) was carried out against Gram-positive bacteria (Staphylococcus aureus, Streptococcus pyogenes), Gramnegative bacteria (Escherichia coli, Pseudomonas aeruginosa) and fungi (Candida albicans, Aspergillus niger, Aspergillus clavatus) using serial broth dilution method. On the basis of statistical analysis, it is observed that these compounds gave significant co-relation. Newly synthesized compounds 5e, 5f, 5g, 5i and 5l showed significant potency against different microbial strains.

  16. Design, synthesis and antifungal activities of novel strobilurin derivatives containing pyrimidine moieties

    Zhang, Xiang; Geo, Yongxin; Liu, Huijun; Guo, Baoyuan; Wang, Huili [Research Center for Eco-Environmental Sciences/Chinese Academy of Sciences, Beijing (China)

    2012-04-15

    Strobilurins are one of the most important classes of agricultural fungicides. To discover new strobilurin derivatives with high activity against resistant pathogens, a series of novel β-methoxy acrylate analogues were designed and synthesized by integrating substituted pyrimidine with a strobilurin pharmacophore. The compounds were confirmed and characterized by infrared, {sup 1}H nuclear magnetic resonance, elemental analysis and mass spectroscopy. The bioassays indicated that most of the compounds (1a-1h) exhibited potent antifungal activities against Colletotrichum orbicular, Botrytis cinerea Pers and Protoporphyria caps ici Leon ian at the concentration of 50 μg/mL. Exhilaratingly, compound 1d (R=3-trifluoromethylphenyl) showed better antifungal activity against all the tested fungi than the commercial stilbenetriol fungicide azoxystrobin.

  17. Design, synthesis and antifungal activities of novel strobilurin derivatives containing pyrimidine moieties

    Strobilurins are one of the most important classes of agricultural fungicides. To discover new strobilurin derivatives with high activity against resistant pathogens, a series of novel β-methoxy acrylate analogues were designed and synthesized by integrating substituted pyrimidine with a strobilurin pharmacophore. The compounds were confirmed and characterized by infrared, 1H nuclear magnetic resonance, elemental analysis and mass spectroscopy. The bioassays indicated that most of the compounds (1a-1h) exhibited potent antifungal activities against Colletotrichum orbicular, Botrytis cinerea Pers and Protoporphyria caps ici Leon ian at the concentration of 50 μg/mL. Exhilaratingly, compound 1d (R=3-trifluoromethylphenyl) showed better antifungal activity against all the tested fungi than the commercial stilbenetriol fungicide azoxystrobin

  18. Effect of the third π ∗ resonance on the angular distributions for electron-pyrimidine scattering

    Mašín, Zdeněk; Gorfinkiel, Jimena D.

    2016-07-01

    We present a detailed analysis of the effect of the well known third π∗ resonance on the angular behaviour of the elastic cross section in electron scattering from pyrimidine. This resonance, occurring approximately at 4.7 eV, is of mixed shape and core-excited character. Experimental and theoretical results show the presence of a peak/dip behaviour in this energy range, that is absent for other resonances. Our investigations show that the cause of the peak/dip is an interference of background p-wave to p-wave scattering amplitudes with the amplitudes for resonant scattering. The equivalent resonance in pyrazine shows the same behaviour and the effect is therefore likely to appear in other benzene-like molecules. Contribution to the Topical Issue "Advances in Positron and Electron Scattering", edited by Paulo Limao-Vieira, Gustavo Garcia, E. Krishnakumar, James Sullivan, Hajime Tanuma and Zoran Petrovic.

  19. Micrococcus luteus correndonucleases. II. Mechanism of action of two endonucleases specific for DNA containing pyrimidine dimers

    Py--Py correndonucleases I and II from Micrococcus luteus act exclusively on thymine-thymine, cytosine-cytosine, and thymine-cytosine cyclobutyl dimers in DNA, catalyzing incision 5' to the damage and generating 3'-hydroxyl and 5'-phosphoryl termini. Both enzymes initiate excision of pyrimidine dimers in vitro by correxonucleases and DNA polymerase I. The respective incised DNAs, however, differ in their ability to act as substrate for phage T4 polynucleotide ligase or bacterial alkaline phosphatase, suggesting that each endonuclease is specific for a conformationally unique site. The possibility that their respective action generates termini which represent different degrees of single strandedness is suggested by the unequal protection by Escherichia coli binding protein from the hydrolytic action of exonuclease VII

  20. Evidence that pyrimidine dimers in DNA can give rise to tumors

    Hart, R.W.; Setlow, R.B.; Woodhead, A.D.

    1977-12-01

    The Amazon molly, Poecilia formosa, is a small fish that grows in clones. Hence, cells from one animal may be transplanted to another without danger of rejection. Cells from thyroid and adjacent tissue were irradiated with uv light in vitro and injected into the abdominal cavity of isogeneic recipients. At appropriate uv doses and numbers of cells injected, all recipients showed exuberant thyroid proliferation. We give arguments and data indicating that the proliferation is a tumor, not a goitrogenic response. If the uv irradiation is followed, but not preceded, by photoreactivating illumination, the yield of thyroid growths is markedly decreased. Because other investigations have shown that photoreactivation monomerizes uv-induced cyclobutylpyrimidine dimers in DNA and does not affect other photoproducts, our data indicate that pyrimidine dimers in DNA can give rise to tumors.

  1. Radio labeling with preassigned frequencies.

    2004-01-01

    A radio labeling of a graph G is an assignment of pairwise distinct, positive integer labels to the vertices of G such that labels of adjacent vertices differ by at least $2$. The radio labeling problem (RL) consists in determining a radio labeling that minimizes the maximum label that is used (the so-called span of the labeling). RL is a well-studied problem, mainly motivated by frequency assignment problems in which transmitters are not allowed to operate on the same frequency channel. We c...

  2. Radioactive labelling of peptidic hormones

    The labelling of peptidic hormones requires stability, specificity and sensitivity of the label. Introduction of a radioactive atome is one way to satisfy these criteria. Several processes have been described to prepare radioactive TRF: synthesis of the peptide with labelled aminoacids or introduction of the label into the hormone. In that approach, tritium can be substituted in the imidazole ring, via precursors activating the proper carbon. Monoiodo TRF leads essentially to tritium labelling of the 5 positions whereas monoazo TRF allows the preparation of 3H TRF labelled in the 2 positions. Di-substituted TRF leads to labelling into the 2 and 5 carbons. Labelled analogs of TRF can be prepared with labelled iodine; further developments of peptide labelling, will be presented. In particular, the homolytic scission of the C-iodine, bond by photochemical activation. The nascent carbon radical can be stabilized by a tritiated scavenger. This approach eliminates the use of heavy metal catalysts

  3. One pyrimidine dimer inactivates expression of a transfected gene in xeroderma pigmentosum cells

    The authors have developed a host cell reactivation assay of DNA repair utilizing UV-treated plasmid vectors. The assay primarily reflects cellular repair of transcriptional activity of damaged DNA measured indirectly as enzyme activity of the transfected genes. They studied three plasmids (pSV2cat, 5020 base pairs; pSV2catSVgpt, 7268 base pairs; and pRSVcat, 5027 base pairs) with different sizes and promoters carrying the bacterial cat gene (CAT, chloramphenicol acetyltransferase) in a construction that permits cat expression in human cells. All human simian virus 40-transformed cells studied expressed high levels of the transfected cat gene. UV treatment of the plasmids prior to transfection resulted in differential decrease in CAT activity in different cell lines. With pSV2catSVgpt, UV inactivation of CAT expression was greater in the xeroderma pigmentosum group A and D lines than in the other human cell lines tested. The D0 of the CAT inactivation curve was 50 J X m-2 for pSV2cat and for pRSVcat in the xeroderma pigmentosum group A cells. The similarity of the D0 data in the xeroderma pigmentosum group A cells for three plasmids of different size and promoters implies they all have similar UV-inactivation target size. UV-induced pyrimidine dimer formation in the plasmids was quantified by assay of the number of UV-induced T4 endonuclease V-sensitive sites. In the most sensitive xeroderma pigmentosum cells, with all three plasmids, one UV-induced pyrimidine dimer inactivates a target of about 2 kilobases, close to the size of the putative CAT mRNA

  4. Bis(2,4,6-tri-amino-pyrimidin-1-ium) sulfate penta-hydrate.

    Nimthong, Ruthairat; Chamchong, Siva; Pakawatchai, Chaveng; Mokhagul, Jedsada; Wattanakanjana, Yupa

    2013-01-01

    The asymmetric unit of the title salt, 2C4H8N5 (+)·SO4 (2-)·5H2O, contains four 2,4,6-tri-amino-pyrimidinium (TAPH(+)) cations, two sulfate anions and ten lattice water mol-ecules. Each two of the four TAPH(+) cations form dimers via N-H⋯N hydrogen bonds between the amino groups and the unprotonated pyrimidine N atoms [graph-set motif R 2 (2)(8)]. The (TAPH(+))2 dimers, in turn, form slightly offset infinite π-π stacks parallel to [010], with centroid-centroid distances between pyrimidine rings of 3.5128 (15) and 3.6288 (16) Å. Other amino H atoms, as well as the pyrimidinium N-H groups, are hydrogen-bonded to sulfate and lattice water O atoms. The SO4 (2-) anions and water mol-ecules are inter-connected with each other via O-H⋯O hydrogen bonds. The combination of hydrogen-bonding inter-actions and π-π stacking leads to the formation of a three-dimensional network with alternating columns of TAPH(+) cations and channels filled with sulfate anions and water mol-ecules. One of the sulfate anions shows a minor disorder by a ca 37° rotation around one of the S-O bonds [occupancy ratio of the two sets of sites 0.927 (3):0.073 (3)]. One water mol-ecule is disordered over two mutually exclusive positions with an occupancy ratio of 0.64 (7):0.36 (7). PMID:24109349

  5. N-Cyclohexyl-2-(5-fluoro-1H-indol-3-yl-2-oxoacetamide

    Dan-Li Tian

    2011-07-01

    Full Text Available In title compound, C16H17FN2O2, the cyclohexane ring adopts a chair conformation.. The crystal packing is stabilized by weak π–π stacking interactions [centroid–centroid distance = 3.503 (5 Å] and intermolecular C—H...O, N—H...O and N—H...F hydrogen-bond interactions.

  6. Diaquabis(5-fluoro-2-hydroxybenzoato-κO1zinc(II

    2009-03-01

    Full Text Available The title compound, [Zn(C7H4FO32(H2O2], is a monomeric ZnII complex. The ZnII atom, which lies on a twofold rotation axis, is situated in a distorted tetrahedral environment composed of two monodentate carboxlyate O atoms and two water O atoms. O—H...O hydrogen bonds link these units, forming sheets that are stacked along the c axis.

  7. Glycosyltransferase Mechanisms: Impact of a 5-Fluoro Substituent in Acceptor and Donor Substrates on Catalysis†

    Hartman, Matthew C. T.; Jiang, Songmin; Jeffrey S. Rush; Waechter, Charles J.; Coward, James K

    2007-01-01

    In glycosyltransferase-catalyzed reactions a new carbohydrate-carbohydrate bond is formed between a carbohydrate acceptor and the carbohydrate moiety of either a sugar nucleotide or lipid-linked saccharide donor. It is currently believed that most glycosyltransferase-catalyzed reactions occur via an electrophilic activation mechanism with the formation of an oxocarbenium ion-like transition state, a hypothesis that makes clear predictions regarding the charge development on the donor (strong ...

  8. Computational analysis for antimicrobial active pyrano[2,3-d]pyrimidine derivatives on the basis of theoretical and experimental ground

    Ajmal R. Bhat

    2016-06-01

    Full Text Available Annulated pyrano[2,3-d]pyrimidine derivatives were synthesized with methoxy, hydroxyl, nitrile and bromine substituents in its skeleton and correlated by electronic effect of substituents on the magnitude of antimicrobial activity. The different electron donating and electron withdrawing substituents of the pyrano[2,3-d]pyrimidine derivatives exerted positive influence on its antimicrobial activity against some Gram positive and Gram negative bacteria such as, Bacillus cereus, Staphylococcus aureus, Klebsiella pneumonia, Pseudomonas aureus and Escherichia coli, respectively. Antibacterial screening revealed that the presence of heteroaryl, cyano and amino groups on pyrano[2,3-d]pyrimidine skeleton increases its penetrating power on bacterial cell wall and becomes more biologically active. All the pyrano[2,3-d]pyrimidine derivatives were characterized by IR, 1H NMR, 13C NMR and mass spectra.

  9. Synthesis, characterization and biological activity of new cyclization products of 3-(4-substituted benzylidene)-2-pyrido[1,2-]pyrimidine 2,4-(3)-diones

    Abha Bishnoi; Suruchi Singh; Anil K Tiwari; Krishna Srivastava; Ram Raghuvir; Chandrakant M Tripathi

    2013-03-01

    A method is presented for the synthesis of 4-(substituted phenyl)-3-(3-substituted phenyl)4-spiro[isoxazole-5,3'-pyrido[1,2-]pyrimidine]-2',4'-dione (3), 3-(4-substituted phenyl)-3-isoxazole[3, 4-]pyrido[1,2-]pyrimidin-4-(3a)-one (4) and 3-(4-substituted phenyl) 3,3a-dihydropyrazolo[3,4-]pyrido[1,2-]pyrimidin-4-(2)-one (5) which consists of the conversion of 2-pyrido[1,2-]pyrimidine-2,4(3)-dione (1) to chalcones (2) and their 1,3-dipolar cycloaddition with appropriate aldoximes to give spiro compounds and heterocyclization using amines to yield isoxazolines and pyrazolines. All the compounds were screened for their antimicrobial and antitubercular activity.

  10. Synthesis of labeled compounds

    Intermediate compounds labeled with 13C included methane, sodium cyanide, methanol, ethanol, and acetonitrile. A new method for synthesizing 15N-labeled 4-ethylsulfonyl-1-naphthalene-sulfonamide was developed. Studies were conducted on pathways to oleic-1-13C acid and a second pathway investigated was based on carbonation of 8-heptadecynylmagnesium bromide with CO2 to prepare sterolic acid. Biosynthetic preparations included glucose-13C from starch isolated from tobacco leaves following photosynthetic incubation with 13CO2 and galactose-13C from galactosylglycerol-13C from kelp. Research on growth of organisms emphasized photosynthetic growth of algae in which all cellular carbon is labeled. Preliminary experiments were performed to optimize the growth of Escherichia coli on sodium acetate-13C

  11. Fluorine-18 labelled compounds

    The work presented in this thesis deals with the problems involved in the adaption of reactor-produced fluorine-18 to the synthesis of 18F-labelled organic fluorine compounds. Several 18F-labelling reagents were prepared and successfully applied. The limitations to the synthetic possibilities of reactor-produced fluoride-18 become manifest in the last part of the thesis. An application to the synthesis of labelled aliphatic fluoro amino acids has appeared to be unsuccessful as yet, although some other synthetic approaches can be indicated. Seven journal articles (for which see the availability note) are used to compose the four chapters and three appendices. The connecting text gives a survey of known 18F-compounds and methods for preparing such compounds. (Auth.)

  12. PET imaging of HSV1-tk mutants with acquired specificity toward pyrimidine- and acycloguanosine-based radiotracers

    The aim of this study was to create an alternative mutant of the herpes simplex virus type 1 thymidine kinase (HSV1-tk) reporter gene with reduced phosphorylation capacity for acycloguanosine derivatives, but not pyrimidine-based compounds that will allow for successful PET imaging. A new mutant of HSV1-tk reporter gene, suitable for PET imaging using pyrimidine-based radiotracers, was developed. The HSV1-tk mutant contains an arginine-to-glutamine substitution at position 176 (HSV1-R176Qtk) of the nucleoside binding region of the enzyme. The mutant-gene product showed favorable enzymatic characteristics toward pyrimidine-based nucleosides, while exhibiting reduced activity with acycloguanosine derivatives. In order to enhance HSV1-R176Qtk reporter activity with pyrimidine-based radiotracers, we introduced the R176Q substitution into the more active HSV1-sr39tk mutant. U87 human glioma cells transduced with the HSV1-R176Qsr39tk double mutant reporter gene showed high 3H-FEAU pyrimidine nucleoside and low 3H-penciclovir acycloguanosine analog uptake in vitro. PET imaging also demonstrated high 18F-FEAU and low 18F-FHBG accumulation in HSV1-R176Qsr39tk+ xenografts. The feasibility of imaging two independent nucleoside-specific HSV1-tk mutants in the same animal with PET was demonstrated. Two opposite xenografts expressing the HSV1-R176Qsr39tk reporter gene and the previously described acycloguanosine-specific mutant of HSV1-tk, HSV1-A167Ysr39tk reporter gene, were imaged using a short-lived pyrimidine-based 18F-FEAU and an acycloguanosine-based 18F-FHBG radiotracer, respectively, administered on 2 consecutive days. We conclude that in combination with acycloguanosine-specific HSV1-A167Ysr39tk reporter gene, a HSV1-tk mutant containing the R176Q substitution could be used for PET imaging of two different cell populations or concurrent molecular biological processes in the same living subject. (orig.)

  13. Synthesis of new pyrrole, pyrazole, pyrimidine and pyrrolopyrimidine derivatives carrying a sulfonamide moiety of expected antitumor activity with studying the synergistic effect of γ-irradiation

    In a search for new cytotoxic agents with improved antitumor activity, some new pyrrole, pyrazole pyrimidine and pyrrolo[2,3-d] pyrimidine derivatives bearing sulfonamide moiety were synthesized. All the newly synthesized compound were subjected to in-vitro cytotoxic screening, also the synergism of the synthesized compounds with radiation was studies. These new compounds were docked in the active site of the carbonic anhydrase enzyme.

  14. Synthesis and evaluation of a series of pyrimidine substituted 1,3,4-oxadiazole derivatives as antimicrobial and anti-inflammatory agents

    Sanath Kumar Goud Palusa; Rajgopal H.Udupi; Himabindu V; Ajjanna M Sridhara

    2011-01-01

    Novel pyrimidine substituted 1,3,4-oxadiazole derivatives (11a-k) were synthesized from the condensation of different substituted aromatic carboxylic acids with substituted pyrimidine carboxy hydrazide using POCl3 as condensing agent. Their structures were characterized by physical and spectral studies. The synthesized compounds were evaluated for their in vitro antimicrobial and anti-inflammatory activity. Some of the newly synthesized compounds showed good antimicrobial and anti-inflammator...

  15. Synthesis and evaluation of a series of pyrimidine substituted 1,3,4-oxadiazole derivatives as antimicrobial and anti-inflammatory agents

    Sanath Kumar Goud Palusa

    2011-01-01

    Full Text Available Novel pyrimidine substituted 1,3,4-oxadiazole derivatives (11a-k were synthesized from the condensation of different substituted aromatic carboxylic acids with substituted pyrimidine carboxy hydrazide using POCl3 as condensing agent. Their structures were characterized by physical and spectral studies. The synthesized compounds were evaluated for their in vitro antimicrobial and anti-inflammatory activity. Some of the newly synthesized compounds showed good antimicrobial and anti-inflammatory activities.

  16. Semantic Role Labeling

    Palmer, Martha; Xue, Nianwen

    2011-01-01

    This book is aimed at providing an overview of several aspects of semantic role labeling. Chapter 1 begins with linguistic background on the definition of semantic roles and the controversies surrounding them. Chapter 2 describes how the theories have led to structured lexicons such as FrameNet, VerbNet and the PropBank Frame Files that in turn provide the basis for large scale semantic annotation of corpora. This data has facilitated the development of automatic semantic role labeling systems based on supervised machine learning techniques. Chapter 3 presents the general principles of applyin

  17. Hypoxia stimulates binding of a cytoplasmic protein to a pyrimidine-rich sequence in the 3'-untranslated region of rat tyrosine hydroxylase mRNA.

    Czyzyk-Krzeska, M F; Dominski, Z; Kole, R; Millhorn, D E

    1994-04-01

    Reduced oxygen tension (hypoxia) induces a 3-fold increase in stability of mRNA for tyrosine hydroxylase (TH), the rate-limiting enzyme in catecholamine synthesis, in the pheochromocytoma (PC12) clonal cell line. To investigate the possibility that RNA-protein interactions are involved in mediating this increase in stability, RNA gel shift assays were performed using different fragments of labeled TH mRNA and the S-100 fraction of PC12 cytoplasmic protein extracts. We identified a sequence within the 3'-untranslated region of TH mRNA that binds cytoplasmic protein. RNase T1 mapping revealed that the protein was bound to a 28 nucleotide long sequence that is located between bases 1551-1579 of TH mRNA. Moreover, protein binding to this fragment was prevented with an antisense oligonucleotide directed against bases 1551-1579 and subsequent RNase H digestion. This fragment of the 3'-untranslated region of TH mRNA is rich in pyrimidine nucleotides, and the binding of cytoplasmic protein to this fragment was reduced by competition with other polypyrimidine sequences including poly(C) but not poly(U) polymers. The binding of the protein to TH mRNA was increased when cytoplasmic proteins were extracted from PC12 cells exposed to hypoxia (5% O2) for 24 h. Electrophoresis of the UV cross-linked RNA-protein complex on SDS-polyacrylamide gel electrophoresis revealed a complex of 74 kDa. The potential role of this protein-TH mRNA interaction in regulation of TH mRNA stability during hypoxia is discussed. PMID:7908289

  18. Novel (2,6-difluorophenyl)(2-(phenylamino)pyrimidin-4-yl)methanones with restricted conformation as potent non-nucleoside reverse transcriptase inhibitors against HIV-1.

    Šimon, Petr; Baszczyňski, Ondřej; Šaman, David; Stepan, George; Hu, Eric; Lansdon, Eric B; Jansa, Petr; Janeba, Zlatko

    2016-10-21

    To elucidate the structure-geometry-activity relationship in diarylpyrimidine family (DAPYs) containing carbonyl linker between the central pyrimidine core and phenyl type B-arm, a series of (2,6-difluorophenyl)(2-(phenylamino)pyrimidin-4-yl)methanones was designed, prepared and tested for their anti-HIV-1 activity. The carbonyl linker bearing B phenyl arm was successfully attached at both C-2 and C-4 positions of the central pyrimidine ring using a new synthetic approach. Further modifications of target compounds are present at C-5 position of the pyrimidine ring. In vitro anti-HIV-1 activity study performed on a series of 22 compounds confirmed the crucial importance of both conformational rigidity between phenyl B arm and the pyrimidine core linked through the carbonyl bridge, as well as presence of fluoro substituents in ortho-positions of phenyl B moiety. The most potent derivative of the series, compound 17, having almost perpendicular angle within the two planes made from the B aromatic arm and the pyrimidine ring, exhibited low nanomolar anti-HIV-1 activity (EC50 = 4 nM) with no significant toxicity (CC50 > 57.1 μM). PMID:27371922

  19. Radioactively labelled porphyrin derivatives

    Radioactive labelling of guanidine bearing tetraphenylporphyrin and Dy-texaphyrin with 166Ho and 90Y is described. UV-VIS absorption spectrometry was used to describe porphyrin and texaphyrin, including their behaviour over a wide pH range. This technique also provided preliminary information about the complexation of holmium and yttrium with porphyrin and texaphyrin. The labelling yield of the macrocyclic molecules depends on the pH of the reaction mixture, metal-to-ligand ratio and time of incubation. The optimum reaction conditions for the formation of radioactive complexes of porphyrin and texaphyrin were determined by thin layer chromatography combined with beta activity measurement. The ability of porphyrin derivatives to bind anions was also examined. Our experiments were focused on perrhenate ion (ReO4-) because radiopharmaceuticals labeled with 186Re and 188Re play an important role in the therapy of many tumorous diseases. The possibility of using the ReO4- anion directly for labeling without reduction to a lower oxidation state can simplify considerably the preparation of the radiotherapeutic pharmaceuticals. Neither UV-Vis spectrometry nor TLC gave evidence of any incorporation of the ReO4- anion into the porphyrin ring

  20. Labeling of herbicide femesafen

    5-[2-chroo-4-(trifluoromethyl ) phenoxy]-N-(methyl sulphonyl )-2-niorobenzamide [femesafen] was labeled by six steps. Radio-chemical yield was 19.15%. TLC analysis of the final product showed that the radiochemical purity is not less than 99%. (authors)

  1. Waisda?: video labeling game

    Hildebrand, M.; Brinkerink, M.; Gligorov, R.; Steenbergen, M. van; Huijkman, J.; Oomen, J.

    2013-01-01

    The Waisda? video labeling game is a crowsourcing tool to collect user-generated metadata for video clips. It follows the paradigm of games-with-a-purpose, where two or more users play against each other by entering tags that describe the content of the video. Players score points by entering the sa

  2. Understanding Food Labels

    ... girls Eating healthy at restaurants Special food issues Vegetarian eating Eating for strong bones Quiz: Food Facts Links to more information girlshealth glossary girlshealth.gov home http://www.girlshealth.gov/ Home Nutrition Healthy eating for girls Understanding food labels Understanding ...

  3. Stabilization of labelled compounds

    This invention concerns a composition including a labelled compound, and the vitamin B 12. This vitamin gives a red colour to the solution and stabilize it radiochemically, allowing to transport the solution at ambient temperature and a storage at 4 degrees celsius. (N.C.). 5 refs

  4. Genetic algorithms for map labeling

    Dijk, Steven Ferdinand van

    2002-01-01

    Map labeling is the cartographic problem of placing the names of features (for example cities or rivers) on the map. A good labeling has no intersections between labels. Even basic versions of the problem are NP-hard. In addition, realistic map-labeling problems deal with many cartographic constraints, which pose more demands on how the labels should be placed in relation to their surroundings. For example, a label is preferably placed above and to the right of a city. These two aspects (comb...

  5. Selective deuterium exchange of protons of C-methyl groups in azine (mono- and bicyclic pyrimidine) systems

    In 1H NMR spectrum of 1,2-dihydro-2-imino-1,4,6-trimethylpyrimidine, registered after addition of CD3ONa, the basic deuterium exchange of protons of only C-methyl groups of pyrimidinium salt proceeded easily, quantitatively and selectively. Similar exchange under the action of CD3ONa was also observed in spectra of annealed pyrimidines 2-methyl(phenyl)-7-amino-4,5-dimethylpyrazolo [1,5-a] pyrimidinium iodides. The basic deuterium exchange was shown to affect protons of only C5-methyl group of pyrimidine. The position of the methyl group subjected to isotope exchange was unambiguously determined by NOESY two-dimensional spectroscopy. Deuterium exchange was also confirmed mass-spectrometrically

  6. TD-DFT Investigation of the Magnetic Circular Dichroism Spectra of Some Purine and Pyrimidine Bases of Nucleic Acids

    Fahleson, Tobias; Kauczor, Joanna; Norman, Patrick;

    2015-01-01

    We present a computational study of the magnetic circular dichroism (MCD) spectra in the 200–300 nm wavelength region of purine and its derivative hypoxanthine, as well as of the pyrimidine bases of nucleic acids uracil, thymine, and cytosine, using the B3LYP and CAM–B3LYP functionals. Solvent...... effects are investigated within the polarizable continuum model and by inclusion of explicit water molecules. In general, the computed spectra are found to be in good agreement with the experimental ones, apart from some overall blue shifts. Both the pseudo-A term shape of the MCD spectra of the purines...... and the B term shape of the spectra of pyrimidine bases are reproduced. Our calculations also correctly reproduce the reversed phase of the MCD bands in purine compared to that of its derivatives present in nucleic acids. Solvent effects are sizable and system specific, but they do not in general...

  7. QSAR study of some pyrazolo[3,4-d]pyrimidine derivatives as the c-Src inhibitors

    Shukla, Bindesh Kumar; Yadava, Umesh

    2016-05-01

    Two dimensional quantitative structure activity relationship (QSAR) studies have been carried out on a series of 42 pyrazolo[3,4-d]pyrimidine derivatives to find out the structural requirements for the inhibition of c-SRC phosphorilation. The best predictions were obtained using Heuristic and Best MLR methods from the model where 33 compounds were considered in the training set and the remaining 9 in the test set. Both Best MLR and Heuristic methods indicate that squared correlation coefficient for training and test sets are very close to observed biological activities which designate the good correlation between the experimental and predicted activity. The results that are obtained from 2D-QSAR studies may provide useful insights into the roles of various substitution patterns on the pyrazolo[3,4-d]pyrimidine core and may also help to design more potent compounds.

  8. Cytotoxicity of three new triazolo-pyrimidine derivatives against the plant trypanosomatid: Phytomonas sp. isolated from Euphorbia characias

    Rosa Magán

    2004-10-01

    Full Text Available There is no effective chemotherapy against diseases caused by Phytomonas sp., a plant trypanosomatid responsible for economic losses in major crops. We tested three triazolo-pyrimidine complexes [two with Pt(II, and another with Ru(III] against promastigotes of Phytomonas sp. isolated from Euphorbia characias. The incorporation of radiolabelled precursors, ultrastructural alterations and changes in the pattern of metabolite excretion were examined. Different degrees of toxicity were found for each complex: the platinun compound showed an inhibition effect on nucleic acid synthesis, provoking alterations on the levels of mitochondria, nucleus and glycosomes. These results, together with others reported previously in our laboratory about the activity of pyrimidine derivatives, reflect the potential of these compounds as agents in the treatment of Phytomonas sp.

  9. Synthesis of Some Novel Pyrazolo[1,5-a]pyrimidine Derivatives and Their Application as Disperse Dyes

    Alya M. Al-Etaibi

    2011-06-01

    Full Text Available A series of novel monoazo-disperse dyes containing pyrazolo[1,5-a]pyrimidine structures were synthesized starting with the coupling reaction between ethyl cyanoacetate and 4-hydroxybenzenediazonium chloride, followed by treatment of the resulting hydrazone product with hydrazine hydrate. The pyrazolohydrazone 6 is then treated with either 2,4-pentandione and enaminonitrile or aryl-substituted enaminoketones to give the target pyrazolo[1,5-a]pyrimidine dyes 7 and 15a-d. Structural assignments to the dyes were made using NMR spectroscopic methods. A new high temperature method, using microwave heating, was employed to apply these dyes to polyester fibers. Most of the dyed fabrics tested displayed moderate light fastness and excellent washing fastness properties.

  10. Crystal structure of 1-methyl-4-methylsulfanyl-1H-pyrazolo[3,4-d]pyrimidine

    Mohammed El Fal

    2014-12-01

    Full Text Available In the title compound, C7H8N4S, the non-H atoms of the pyrazolo[3,4-d]pyrimidine ring system and the methylsulfanyl group lie on a crystallographic mirror plane. In the crystal, molecules are linked via a number of π–π interactions [centroid–centroid distances vary from 3.452 (7 to 3.6062 (8 Å], forming a three-dimensional structure.

  11. Structural Characterization of RNA Polymerase II Complexes Arrested by a Cyclobutane Pyrimidine Dimer in the Transcribed Strand of Template DNA*

    Tornaletti, Silvia; Reines, Daniel; Hanawalt, Philip C.

    1999-01-01

    We have characterized the properties of immunopurified transcription complexes arrested at a specifically located cyclobutane pyrimidine dimer (CPD) using enzymatic probes and an in vitro transcription system with purified RNA polymerase II (RNAP II) and initiation factors. To help understand how RNAP II distinguishes between a natural impediment and a lesion in the DNA to initiate a repair event, we have compared the conformation of RNAP II complexes arrested at a CPD with complexes arrested...

  12. Ethyl 7-(4-bromophenyl-5-trifluoromethyl-4,7-dihydrotetrazolo[1,5-a]pyrimidine-6-carboxylate

    Shi-De Shen

    2010-09-01

    Full Text Available In the title compound, C14H11BrF3N5O2, the pyrimidine ring adopts a flattened envelope conformation with sp3-hybridized carbon as the flap [deviation = 0.177 (3 Å]. The dihedral angle between tetrazole and bromophenyl rings is 84.3 (1°. In the crystal, molecules are linked into centrosymmetric dimers by pairs of N—H...N hydrogen bonds.

  13. Syntheses of pyrimidine acyclic nucleoside phosphonates as potent inhibitors of thymidine phosphorylase (PD-ECGF) from SD-lymphoma

    Pomeisl, Karel; Votruba, Ivan; Holý, Antonín; Pohl, Radek

    2007-01-01

    Roč. 26, 8/9 (2007), s. 1025-1028. ISSN 1525-7770. [International Roundtable /17./. Bern, 03.09.2006-07.09.2006] R&D Projects: GA MŠk 1M0508 Grant ostatní: Descartes Prize(XE) HPAW-CT-2002-9001 Institutional research plan: CEZ:AV0Z40550506 Keywords : acyclic nucleoside phosphonates * thymidine phosphorylase * pyrimidines * FPMP derivatives * fluorination Subject RIV: CC - Organic Chemistry Impact factor: 0.723, year: 2007

  14. Highly diastereoselective domino synthesis of 6-spirosubstituted pyrido[2,3-d]pyrimidine derivatives in water.

    Jiang, Bo; Cao, Long-Ji; Tu, Shu-Jiang; Zheng, Wen-Rui; Yu, Hai-Zhu

    2009-01-01

    A highly diastereoselective domino reaction of 2,6-diaminopyrimidine-4-one with structurally diverse aryl aldehydes and various barbituric acids in water under microwave irradiation is described. The products are 6-spiro-substituted pyrido[2,3-d]pyrimidines with high diastereoselectivities (up to 99: 1) in which the major diastereomer bears a cis relationship between substituents at the 5- and 7-positions. Furthermore, the mechanism for diastereoselectivity was confirmed by DFT (B3LYP) calculations. PMID:19537742

  15. Intramolecular derivatization of 2'-amino-pyrimidine modified RNA with functional groups that is compatible with re-amplification.

    Kujau, M J; Wölfl, S

    1998-01-01

    To expand the scope of nucleic acid aptamers as a tool for precise molecular recognition, functional groups that are not naturally present in nucleic acid molecules are desired. For in vitro selection these new functional groups must be compatible with the selection process. The present method allows the introduction of succinimide activated side chains at internal amino groups of 2'-amino-pyrimidine-RNA in a combinatorial fashion that is compatible with enzymatic re-amplification.

  16. Design, synthesis and antiproliferative activity of novel 2,7-disubstituted triazolo[1,5-a]pyrimidines

    Xin Zhai; Nan Jiang; Ke Liang Zhang; Feng Bao; Ping Gong

    2009-01-01

    In our efforts to identify novel potent anticancer agents, we synthesized a series of 2,7-disubstituted triazolo[1,5-a]pyrimidines (6-16). Their antiproliferative activity against Bel-7402, HT- 1080 and WI-38 cell lines was tested by MTT assay in vitro. Four of the compounds (9-11 and 16) displayed promising antiproliferative activity superior to gefitinib, especially compound 9. A preliminary SAR study of these derivatives was performed.

  17. Molecular mechanisms of pyrimidine dimer excision in Saccharomyces cerevisiae: incision of ultraviolet-irradiated deoxyribonucleic acid in vivo

    A group of genetically related ultraviolet (uv)-sensitive mutants of Saccharomyces cerevisiae has been examined in terms of their survival after exposure to uv radiation, their ability to carry out excision repair or pyrimidine dimers as measured by the loss of sites (pyrimidine dimers) sensitive to a dimer-specific enzyme probe, and in terms of their ability to effect incision of their deoxyribonucleic acid (DNA) during post-uv incubation in vivo (as measured by the detection of single-strand breaks in nuclear DNA). In addition to a haploid RAD+ strain (S288C), 11 different mutants representing six RAD loci (RAD1, RAD2, RAD3, RAD4, RAD14, and RAD18) were examined. Quantitative analysis of excision repair capacity, as determined by the loss of sites in DNA sensitive to an enzyme preparation from M. luteus which is specific for pyrimidine dimers, revealed a profound defect in this parameter in all but three of the strains examined. The rad14-1 mutant showed reduced but significant residual capacity to remove enzyme-sensitive sites as did the rad2-4 mutant. The latter was the only one of three different rad2 alleles examined which was leaky in this respect. The uv-sensitive strain carrying the mutant allele rad18-1 exhibited normal loss of enzyme-sensitive sites consistent with its assignment to the RAD6 rather than the RAD3 epistatic group. All strains having mutant alleles of the RAD1, RAD2, RAD3, RAD4, and RAD14 loci showed no detectable incubation-dependent strand breaks in nuclear DNA after exposure to uv radiation. These experiments suggest that the RAD1, RAD2, RAD3, RAD4 (and probably RAD14) genes are all required for the incision of uv-irradiated DNA during pyrimidine dimer excision in vivo

  18. Multimodality Molecular Imaging of [18F]-Fluorinated Carboplatin Derivative Encapsulated in [111In]-Labeled Liposomes

    Lamichhane, Narottam

    -fluoro-pentyl)-2-methyl malonic acid as the labeling agent to coordinate with the cisplatin aqua complex. It was then used to treat various cell lines and compared with cisplatin and carboplatin at different concentrations ranging from 0.001 microM to 100 microM for 72 hrs and 96 hrs. IC50 values calculated from cell viability indicated that 19F-FCP is a more potent drug than Carboplatin. Manual radiosynthesis and characterization of [18F]-FCP was performed using [18F]-2-(5-fluoro-pentyl)-2-methyl malonic acid with coordination with cisplatin aqua complex. Automated radiosynthesis of [18F]-FCP was optimized using the manual synthetic procedures and using them as macros for the radiosynthesizer. [18F]-FCP was evaluated in vivo with detailed biodistribution studies and PET imaging in normal and KB 3-1 and KB 8-5 tumor xenograft bearing nude mice. The biodistribution studies and PET imaging of [18F]-FCP showed major uptake in kidneys which attributes to the renal clearance of radiotracer. In vivo plasma and urine stability demonstrated intact [18F]-FCP. [ 111In]-Labeled Liposomes was synthesized and physiochemical properties were assessed with DLS. [111In]-Labeled Liposome was evaluated in vivo with detailed pharmacokinetic studies and SPECT imaging. The biodistribution and ROI analysis from SPECT imaging showed the spleen and liver uptake of [111In]-Labeled Liposome and subsequent clearance of activity with time. [18F]-FCP encapsulated [111In]-Labeled Liposome was developed and physiochemical properties were characterized with DLS. [18F]-FCP encapsulated [111In]-Labeled Liposome was used for in vivo dual tracer PET and SPECT imaging from the same nanoconstruct in KB 3-1 (sensitive) and COLO 205 (resistant) tumor xenograft bearing nude mice. PET imaging of [18F]-FCP in KB 3-1 (sensitive) and COLO 205 (resistant) tumor xenograft bearing nude mice was performed. Naked [18F]-FCP and [18F]-FCP encapsulated [ 111In]-Labeled Liposome showed different pharmacokinetic profiles. PET

  19. Analgesic Activity of Some 1,2,4-Triazole Heterocycles Clubbed with Pyrazole, Tetrazole, Isoxazole and Pyrimidine

    Ramdas Bhanudas Pandhare

    2013-02-01

    Full Text Available Purpose: In the present study in vivo analgesic activity of some previously synthesized 1,2,4-triazole derivatives containing pyrazole, tetrazole, isoxazole and pyrimidine ring have been evaluated. Methods: Acetic acid induced writhing method and Hot plate method has been described to study analgesic activity of some 1,2,4-triazole derivatives containing pyrazole, tetrazole, isoxazole and pyrimidine as a pharmacological active lead. Results: Thirty six different derivatives containing 1,2,4-triazole ring were subjected to study their in vivo analgesic activity. Chloro, nitro and methoxy, hydroxy and bromo substituted derivatives showed excellent analgesic activity and dimethylamino, furan and phenyl substituted derivatives showed moderate analgesic activity in both of the methods. Compounds IIIa, IIId, IIIf, IIIi, IIIj, IVa, IVb, IVd, IVf, IVh, IVj IV3a and IIj were found to be superior analgesic agents after screening by Acetic acid induced writhing method. Compounds IIIb, IIId, IIIf, IIIh, IIIj, IVa, IVb, IVd, IVf, IVh, IVi, IV3c, IV3e and IIj were showed analgesic potential after screening of Hot plate method. Conclusion: All tested compounds containing 1,2,4-triazole were found to be promising analgesic agents, for this activity pyrazole, tetrazole, isoxazole and pyrimidine leads might be supported.

  20. Microwave-Assisted Synthesis and Antimicrobial Evaluation of Novel Spiroisoquinoline and Spiropyrido[4,3-d]pyrimidine Derivatives

    Rasha M. Faty

    2015-01-01

    Full Text Available Bromination of N-substituted homophthalimides and tetrahydropyrido[4,3-d]- pyrimidine-5,7-diones produces 4,4-dibromohomophthalimide and 8,8-dibromo-tetrahydropyrido[4,3-d]pyrimidine-5,7-dione derivatives, respectively, that can be used as precursors for spiro derivatives. The dibromo derivatives react with different binucleophilic reagents to produce several spiroisoquinoline and spirotetrahydropyrido[4,3-d]- pyrimidine-5,7-dione derivatives, respectively. Reaction of the dibromo derivatives with malononitrile produces dicyanomethylene derivatives which react with different binucleophiles to produce new spiro derivatives. All new compounds are prepared by using the usual chemical conditions and microwave assisted conditions. The latter conditions improved the reaction yields, reduced reaction times and ameliorated the effects on the surrounding environment as the reactions are carried out in closed systems. Structures of the newly synthesized compounds are proved using spectroscopic methods such as IR, MS, 1H-NMR and 13C-NMR and elemental analyses. Some of the newly synthesized compounds were tested for their antimicrobial activities, whereby four of them showed moderate activities and the rest showed low or no activities towards the investigated species.

  1. Photoreactivation of pyrimidine dimers generated by a photosensitized reaction in RNA of the Smittia sp. embryos after UV-irradiation

    Mechanisms of biological effects resulting from the irradiation of Smittia sp. embryos in an early stage of developmentment with UV rays with the wave-length of 265, 285 and 295 nm are investigated. It is shown that the cessation of development, deceleration of protein synthesis and emergence of additional abdomens after the irradiation of embryos in early stages of development are not connected with the damage of the nucleus but with the formation of pyrimidine dimers in RNA in the cortical layer of ovum cytoplasm. At first, the energy of UV rays with the given wave-lengths is accepted in the cell by molecules-photosensitizers. It is shown for the first time that pyrimidine dimers generated in RNA can be photoreactivated on exposure of cells to light. Maternal RNA accumulated during oogenesis play an important role in the early embryogeny of insects and other animals ova developing in the sunlight. Therefore, the protection of embryo RNA from solar UV irradiation damage is provided for by the mechanisms of RNA pyrimidine dimers photoreactivation resulted from the sunlight long waves

  2. Spin labels. Applications in biology

    The main applications of spin labels in the study of biomembranes, enzymes, nucleic acids, in pharmacology, spin immunoassay are reviewed along with the fundamentals of the spin label method. 137 references. (author)

  3. Use the Nutrition Facts Label

    ... Features Spokespeople News Archive eNewsletters Calendar Use the Nutrition Facts Label You can help your family eat ... to some of their favorite foods. Use the Nutrition Facts label found on food packages to make ...

  4. Labeling lake water with tritium

    Frederick, B.J.

    1963-01-01

    A method of packaging tritiated water in a manner that facilitates safe handling in environmental labeling operations, and procedures followed in labeling a large body of water with a small volume of tritiated water are described. ?? 1963.

  5. Biochemical and molecular characterization of the pyrimidine biosynthetic enzyme dihydroorotate dehydrogenase from Toxoplasma gondii.

    Hortua Triana, Miryam Andrea; Huynh, My-Hang; Garavito, Manuel F; Fox, Barbara A; Bzik, David J; Carruthers, Vern B; Löffler, Monika; Zimmermann, Barbara H

    2012-08-01

    The pyrimidine biosynthesis pathway in the protozoan pathogen Toxoplasma gondii is essential for parasite growth during infection. To investigate the properties of dihydroorotate dehydrogenase (TgDHOD), the fourth enzyme in the T. gondii pyrimidine pathway, we expressed and purified recombinant TgDHOD. TgDHOD exhibited a specific activity of 84U/mg, a k(cat) of 89s(-1), a K(m)=60μM for l-dihydroorotate, and a K(m)=29μM for decylubiquinone (Q(D)). Quinones lacking or having short isoprenoid side chains yielded lower k(cat)s than Q(D). As expected, fumarate was a poor electron acceptor for this family 2 DHOD. The IC(50)s determined for A77-1726, the active derivative of the human DHOD inhibitor leflunomide, and related compounds MD249 and MD209 were, 91μM, 96μM, and 60μM, respectively. The enzyme was not significantly affected by brequinar or TTFA, known inhibitors of human DHOD, or by atovaquone. DSM190, a known inhibitor of Plasmodium falciparum DHOD, was a poor inhibitor of TgDHOD. TgDHOD exhibits a lengthy 157-residue N-terminal extension, consistent with a potential organellar targeting signal. We constructed C-terminally c-myc tagged TgDHODs to examine subcellular localization of TgDHOD in transgenic parasites expressing the tagged protein. Using both exogenous and endogenous expression strategies, anti-myc fluorescence signal colocalized with antibodies against the mitochondrial marker ATPase. These findings demonstrate that TgDHOD is associated with the parasite's mitochondrion, revealing this organelle as the site of orotate production in T. gondii. The TgDHOD gene appears to be essential because while gene tagging was successful at the TgDHOD gene locus, attempts to delete the TgDHOD gene were not successful in the KU80 background. Collectively, our study suggests that TgDHOD is an excellent target for the development of anti-Toxoplasma drugs. PMID:22580100

  6. Asymmetric purine-pyrimidine distribution in cellular small RNA population of papaya

    Aryal Rishi

    2012-12-01

    Full Text Available Abstract Background The small RNAs (sRNA are a regulatory class of RNA mainly represented by the 21 and 24-nucleotide size classes. The cellular sRNAs are processed by RNase III family enzyme dicer (Dicer like in plant from a self-complementary hairpin loop or other type of RNA duplexes. The papaya genome has been sequenced, but its microRNAs and other regulatory RNAs are yet to be analyzed. Results We analyzed the genomic features of the papaya sRNA population from three sRNA deep sequencing libraries made from leaves, flowers, and leaves infected with Papaya Ringspot Virus (PRSV. We also used the deep sequencing data to annotate the micro RNA (miRNA in papaya. We identified 60 miRNAs, 24 of which were conserved in other species, and 36 of which were novel miRNAs specific to papaya. In contrast to the Chargaff’s purine-pyrimidine equilibrium, cellular sRNA was significantly biased towards a purine rich population. Of the two purine bases, higher frequency of adenine was present in 23nt or longer sRNAs, while 22nt or shorter sRNAs were over represented by guanine bases. However, this bias was not observed in the annotated miRNAs in plants. The 21nt species were expressed from fewer loci but expressed at higher levels relative to the 24nt species. The highly expressed 21nt species were clustered in a few isolated locations of the genome. The PRSV infected leaves showed higher accumulation of 21 and 22nt sRNA compared to uninfected leaves. We observed higher accumulation of miRNA* of seven annotated miRNAs in virus-infected tissue, indicating the potential function of miRNA* under stressed conditions. Conclusions We have identified 60 miRNAs in papaya. Our study revealed the asymmetric purine-pyrimidine distribution in cellular sRNA population. The 21nt species of sRNAs have higher expression levels than 24nt sRNA. The miRNA* of some miRNAs shows higher accumulation in PRSV infected tissues, suggesting that these strands are not totally

  7. Food Labels Tell the Story!

    ... My World From the Label to the Table! Food Labels Tell the Story! What is in food? Food provides your body with all of the ... your food choices. Nutrition Facts—the Labels on Food Products Beginning in 1994, the US government began ...

  8. Isotopically labelled benzodiazepines

    This paper reports on the benzodiazepines which are a class of therapeutic agents. Improvements in the analytical methodology in the areas of biochemistry and pharmacology were significant, particularly in the application of chromatographic and spectroscopic techniques. In addition, the discovery and subsequent development of tritium and carbon-14 as an analytical tool in the biological sciences were essentially post-world war II phenomena. Thus, as these new chemical entities were found to be biologically active, they could be prepared in labeled form for metabolic study, biological half-life determination (pharmacokinetics), tissue distribution study, etc. This use of tracer methodology has been liberally applied to the benzodiazepines and also more recently to the study of receptor-ligand interactions, in which tritium, carbon-11 or fluorine-18 isotopes have been used. The history of benzodiazepines as medicinal agents is indeed an interesting one; an integral part of that history is their use in just about every conceivable labeled form

  9. Nomenclature for labelled compounds

    This paper report on isotopically labelled compounds. The first indexing system for isotopically labelled organic compounds is generally credited to Boughton and named after him. An extension of his principles for designating compounds containing hydrogen isotopes has been part of the Chemical Abstracts Service index nomenclature system for many years. After close on five years labor the IUPAC sponsored Commission on Nomenclature of Organic Chemistry presented in 1979 their findings on Isotopically Modified Compounds. The system codified in their rules provides for recognition of various types of isotopic modification and is therefore of more general applicability. Concurrently the rules for the nomenclature of isotopically modified inorganic compounds are developed. These are to be seen as supplementing and extending the guidelines laid down in the IUPAC Inorganic Nomenclature Rules already published

  10. Labelling, Deviance and Media

    Greer, C.

    2014-01-01

    Labelling theory is a perspective that emerged as a distinctive approach to criminology during the 1960s, and was a major seedbed of the radical and critical perspectives that became prominent in the 1970s. It represented the highpoint of an epistemological shift within the social sciences away from positivism – which had dominated criminological enquiry since the late-1800s – and toward an altogether more relativistic stance on the categories and concepts of crime and control. It inspired a ...

  11. Eco-labelling

    Kuna-Marszałek, Anetta

    2016-01-01

    Considering environmental protection requirements in business operations may, in the long run, determine if a lasting comparative advantage can be achieved. That is why our textbook, rich in case studies, identifies not only the threats a business may pose to the environment but stresses the ways of reducing its negative impact. It discusses, among other things, the concept of corporate social responsibility, environmental management systems, methods and the importance of eco-labelling goods ...

  12. Myocardial arterial spin labeling

    Kober, Frank; Jao, Terrence; Troalen, Thomas; Nayak, Krishna S.

    2016-01-01

    Arterial spin labeling (ASL) is a cardiovascular magnetic resonance (CMR) technique for mapping regional myocardial blood flow. It does not require any contrast agents, is compatible with stress testing, and can be performed repeatedly or even continuously. ASL-CMR has been performed with great success in small-animals, but sensitivity to date has been poor in large animals and humans and remains an active area of research. This review paper summarizes the development of ASL-CMR techniques, c...

  13. Isomeric signatures in the fragmentation of pyridazine and pyrimidine induced by fast ion impact

    Wolff, Wania, E-mail: wania@if.ufrj.br; Luna, Hugo; Montenegro, Eduardo C. [Instituto de Física, Universidade Federal do Rio de Janeiro, 21941-972 Rio de Janeiro, RJ (Brazil)

    2015-07-28

    We present fast proton impact induced fragmentations of pyrimidine and pyridazine as an experimental resource to investigate isomeric signatures. Major isomeric imprints are identified for few fragment ions and differences of more than an order of magnitude for the cross sections of fragments of the same mass were measured. The observation of the molecular structure of these isomers gives no apparent indication for the reasons for such substantial differences. It is verified that the simple displacement of the position of one nitrogen atom strongly inhibits or favors the production of some ionic fragment species. The dependency of the fragmentation cross sections on the proton impact energy, investigated by means of time of flight mass spectroscopy and of a model calculation based in first order perturbation theory, allows us to disentangle the complex collision dynamics of the ionic fragments. The proton-induced fragmentation discriminates rather directly the association between a molecular orbital ionization and the fragment-ions creation and abundance, as well as how the redistribution of the energy imparted to the molecules takes place, triggering not only single but also double vacancy and leads to specific fragmentation pathways.

  14. Osmium-Based Pyrimidine Contrast Tags for Enhanced Nanopore-Based DNA Base Discrimination.

    Robert Y Henley

    Full Text Available Nanopores are a promising platform in next generation DNA sequencing. In this platform, an individual DNA strand is threaded into nanopore using an electric field, and enzyme-based ratcheting is used to move the strand through the detector. During this process the residual ion current through the pore is measured, which exhibits unique levels for different base combinations inside the pore. While this approach has shown great promise, accuracy is not optimal because the four bases are chemically comparable to one another, leading to small differences in current obstruction. Nucleobase-specific chemical tagging can be a viable approach to enhancing the contrast between different bases in the sequence. Herein we show that covalent modification of one or both of the pyrimidine bases by an osmium bipyridine complex leads to measureable differences in the blockade amplitudes of DNA molecules. We qualitatively determine the degree of osmylation of a DNA strand by passing it through a solid-state nanopore, and are thus able to gauge T and C base content. In addition, we show that osmium bipyridine reacts with dsDNA, leading to substantially different current blockade levels than exhibited for bare dsDNA. This work serves as a proof of principle for nanopore sequencing and mapping via base-specific DNA osmylation.

  15. High-resolution photoelectron spectra of the pyrimidine-type nucleobases

    Fulfer, K. D.; Hardy, D.; Poliakoff, E. D., E-mail: epoliak@lsu.edu [Department of Chemistry, Louisiana State University, Baton Rouge, Louisiana 70803 (United States); Aguilar, A. A. [Advanced Light Source, Lawrence Berkeley National Laboratory, Berkeley, California 94720 (United States)

    2015-06-14

    High-resolution photoelectron spectra of the gas phase pyrimidine-type nucleobases, thymine, uracil, and cytosine, were collected using synchrotron radiation over the photon energy range 17 ≤ hν ≤ 150 eV. These data provide the highest resolution photoelectron spectra of thymine, uracil, and cytosine published to date. By comparing integrated regions of the energy dependent photoelectron spectra of thymine, the ionization potentials of the first four ionic states of thymine were estimated to be 8.8, 9.8, 10.3, and 10.8 eV. The thymine data also show evidence for low energy shape resonances in three of the outermost valence electronic states. Comparing the uracil spectrum with the thymine spectrum, the four outermost valence electronic states of uracil likely begin at binding energies 9.3, 9.9, 10.5, and 11.0 eV. High-resolution spectra indicate only one tautomeric form of cytosine contributes significantly to the spectrum with the four outermost valence electronic states beginning at binding energies 8.9, 9.9, 10.4, and 10.85 eV.

  16. Gout and hyperuricemia in Japan: perspectives for international research on purines and pyrimidines in man.

    Hosoya, Tatsuo; Ohno, Iwao; Ichida, Kimiyoshi; Peters, Godefridus J

    2011-12-01

    One of the best-known disorders in purine metabolism is accumulation of uric acid leading to gout. Gout is a lifestyle disease, which was nicely illustrated in the joint symposium of the Japanese Society of Gout and Nucleic Acid Metabolism and of the Purine and Pyrimidine Society held in February 2011 in Tokyo, Japan. The westernization of the Japanese diet led to an increase in hyperuricemia in Japanese, which subsequently boosted research in this field, as illustrated in this symposium. As a consequence, Japanese nucleotide research also expanded, leading to the development of not only new drugs for treatment of gout, but also for other diseases such as cancer, viral infections, and cardiovascular diseases. The research on inborn errors led to the identification of various genetic polymorphisms affecting drug metabolism, revealing differences between Asians and non-Asians. Such genetic differences may also affect the enzymatic properties of an enzyme or a transporter, necessitating specific inhibitors. This knowledge will help to introduce personalization of treatment. In this symposium, the interaction between various specialties formed an excellent basis for translational research between these specialties but also from the bench to the clinic. PMID:22132949

  17. Production of pyrimidine dimers in DNA by an incandescent spot lamp

    The electrophoretic analysis of circular DNA substrates exposed to specific nucleases allows the detection of very small numbers of pyrimidine dimers (PD). The authors devised two assays for this purpose. In both cases PD titration was based on the very high specificity for PD of the purified Micrococcus luteus PD endonuclease, a specific probe for the presence of such photoproducts in DNA. The first method depends on the distinct electrophoretic mobilities of supercoiled (RFI) and nicked circular duplex (FRII) DNA on neutral agarose gels. This method allows the detection of up to four PDs per molecule, but only in supercoiled DNA. The second assay depends on the distinct electrophoretic mobilities of single-stranded (ss) molecules of uniform length and smaller reaction products, obtained after digestion with the specific endonuclease. In this procedure, DNA substrates of uniform length, which may be supercoiled, partially relaxed or linear (ss or ds), are exposed to the M. luteus PD endonuclease, after which uncleaved molecules are separated from the other smaller reduction products by electrophoresis. Then the number of PDs per molecule can be expressed as a function of the number of ss molecules left intact after the specific nicking treatment. With circular substrates, the molecule is linearized by using a restriction endonuclease. This assay can detect up to eight PDs per duplex molecule. The authors developed a new biochemical assay for detecting enzymatic photoreactivation of PDs in 254 nm irradiated, nonradioactive supercoiled DNA

  18. Pyrimidine-specific 5' nucleotidase activity in bovine erythrocytes: effect of phlebotomy and lead poisoning

    Erythrocyte pyrimidine-specific 5' nucleotidase (PY5'N) (E.C. 3.1.3.5) was measured in healthy, anemic, and lead-poisoned calves to determine whether low activity of PY5'N is associated with the propensity of cattle to develop basophilic stippling of erythrocytes. Low activity of PY5'N has been associated with basophilic stippling of erythrocytes in persons with inherited hemolytic anemia and with lead poisoning. A radiometric technique, using [14C]cytidine monophosphate as the substrate, was used to measured PY5'N activity. The erythrocytes from 4 healthy calves had much lower activity (mean of 7.1 +/- 1.6 nmols of [14C]cytidine monophosphate hydrolyzed/min/g of hemoglobin) than has been reported for human erythrocytes. The pH response curve of bovine PY5'N was similar to that of the human enzyme, with maximal activity around pH 7. Experimental hemorrhagic anemia in these calves increased PY5'N activity 6-to 7-fold, with peak activity occurring concomitantly with maximum reticulocytosis. Two of the calves were then given lead per os, and the PY5'N activity decreased within 24 hours to base-line values. In the 2 other calves not given lead, the PY5'N activity declined slowly, but did not reach base-line values after 14 days

  19. Divergent functions through alternative splicing: the Drosophila CRMP gene in pyrimidine metabolism, brain, and behavior.

    Morris, Deanna H; Dubnau, Josh; Park, Jae H; Rawls, John M

    2012-08-01

    DHP and CRMP proteins comprise a family of structurally similar proteins that perform divergent functions, DHP in pyrimidine catabolism in most organisms and CRMP in neuronal dynamics in animals. In vertebrates, one DHP and five CRMP proteins are products of six genes; however, Drosophila melanogaster has a single CRMP gene that encodes one DHP and one CRMP protein through tissue-specific, alternative splicing of a pair of paralogous exons. The proteins derived from the fly gene are identical over 90% of their lengths, suggesting that unique, novel functions of these proteins derive from the segment corresponding to the paralogous exons. Functional homologies of the Drosophila and mammalian CRMP proteins are revealed by several types of evidence. Loss-of-function CRMP mutation modifies both Ras and Rac misexpression phenotypes during fly eye development in a manner that is consistent with the roles of CRMP in Ras and Rac signaling pathways in mammalian neurons. In both mice and flies, CRMP mutation impairs learning and memory. CRMP mutant flies are defective in circadian activity rhythm. Thus, DHP and CRMP proteins are derived by different processes in flies (tissue-specific, alternative splicing of paralogous exons of a single gene) and vertebrates (tissue-specific expression of different genes), indicating that diverse genetic mechanisms have mediated the evolution of this protein family in animals. PMID:22649077

  20. Influence of cytosine methylation on ultraviolet-induced cyclobutane pyrimidine dimer formation in genomic DNA

    Rochette, Patrick J. [Division of Pathology, Department of Medical Biology, Universite Laval, Quebec, QC (Canada); Division of Genetics, Department of Pediatrics, Faculty of Medicine and Health Sciences, Universite de Sherbrooke, Sherbrooke, QC (Canada); Department of Therapeutic Radiology, Yale School of Medicine, New Haven, CT (United States); Lacoste, Sandrine [Division of Pathology, Department of Medical Biology, Universite Laval, Quebec, QC (Canada); Division of Genetics, Department of Pediatrics, Faculty of Medicine and Health Sciences, Universite de Sherbrooke, Sherbrooke, QC (Canada); Manitoba Institute of Cell Biology, University of Manitoba, Winnipeg, MB (Canada); Therrien, Jean-Philippe [Division of Pathology, Department of Medical Biology, Universite Laval, Quebec, QC (Canada); Bastien, Nathalie [Division of Pathology, Department of Medical Biology, Universite Laval, Quebec, QC (Canada); Division of Genetics, Department of Pediatrics, Faculty of Medicine and Health Sciences, Universite de Sherbrooke, Sherbrooke, QC (Canada); Brash, Douglas E. [Department of Therapeutic Radiology, Yale School of Medicine, New Haven, CT (United States); Drouin, Regen, E-mail: Regen.Drouin@USherbrooke.ca [Division of Pathology, Department of Medical Biology, Universite Laval, Quebec, QC (Canada); Division of Genetics, Department of Pediatrics, Faculty of Medicine and Health Sciences, Universite de Sherbrooke, Sherbrooke, QC (Canada)

    2009-06-01

    The ultraviolet (UV) component of sunlight is the main cause of skin cancer. More than 50% of all non-melanoma skin cancers and >90% of squamous cell carcinomas in the US carry a sunlight-induced mutation in the p53 tumor suppressor gene. These mutations have a strong tendency to occur at methylated cytosines. Ligation-mediated PCR (LMPCR) was used to compare at nucleotide resolution DNA photoproduct formation at dipyrimidine sites either containing or lacking a methylated cytosine. For this purpose, we exploited the fact that the X chromosome is methylated in females only on the inactive X chromosome, and that the FMR1 (fragile-X mental retardation 1) gene is methylated only in fragile-X syndrome male patients. Purified genomic DNA was irradiated with UVC (254 nm), UVB (290-320 nm) or monochromatic UVB (302 and 313 nm) to determine the effect of different wavelengths on cyclobutane pyrimidine dimer (CPD) formation along the X-linked PGK1 (phosphoglycerate kinase 1) and FMR1 genes. We show that constitutive methylation of cytosine increases the frequency of UVB-induced CPD formation by 1.7-fold, confirming that methylation per se is influencing the probability of damage formation. This was true for both UVB sources used, either broadband or monochromatic, but not for UVC. Our data prove unequivocally that following UVB exposure methylated cytosines are significantly more susceptible to CPD formation compared with unmethylated cytosines.

  1. Influence of cytosine methylation on ultraviolet-induced cyclobutane pyrimidine dimer formation in genomic DNA

    The ultraviolet (UV) component of sunlight is the main cause of skin cancer. More than 50% of all non-melanoma skin cancers and >90% of squamous cell carcinomas in the US carry a sunlight-induced mutation in the p53 tumor suppressor gene. These mutations have a strong tendency to occur at methylated cytosines. Ligation-mediated PCR (LMPCR) was used to compare at nucleotide resolution DNA photoproduct formation at dipyrimidine sites either containing or lacking a methylated cytosine. For this purpose, we exploited the fact that the X chromosome is methylated in females only on the inactive X chromosome, and that the FMR1 (fragile-X mental retardation 1) gene is methylated only in fragile-X syndrome male patients. Purified genomic DNA was irradiated with UVC (254 nm), UVB (290-320 nm) or monochromatic UVB (302 and 313 nm) to determine the effect of different wavelengths on cyclobutane pyrimidine dimer (CPD) formation along the X-linked PGK1 (phosphoglycerate kinase 1) and FMR1 genes. We show that constitutive methylation of cytosine increases the frequency of UVB-induced CPD formation by 1.7-fold, confirming that methylation per se is influencing the probability of damage formation. This was true for both UVB sources used, either broadband or monochromatic, but not for UVC. Our data prove unequivocally that following UVB exposure methylated cytosines are significantly more susceptible to CPD formation compared with unmethylated cytosines.

  2. Cyclobutyl pyrimidine dimer accumulation in relation to UV-B sensitivity in mung bean cultivars

    The purpose of the experiment is to reveal the relationship between cyclobutyl pyrimidine dimers (CPDs) accumulation and UV-B sensitivity in mung bean cultivars. Two mung bean cultivars (Phaseolus raditus L. cv. Qindou-20 and Zhonglü-1) were grown in greenhouse with treatment or without treatment of UV-B radiation (0.4 W * m-2) for four days. The UV-B-induced CPDs in mung bean DNA were quantified by enzyme-linked immunosorbent assay (ELISA) with specific monoclonal antibody and the relationship between CPDs accumulation and the UV-B sensitivity of mung bean seedlings were discussed. The UV-B-induced inhibition of the biomass and net photosynthetic rate of the primary leaves of cultivar Zhonglü-1 were respectively lower than that of cultivar Qindou-20, so that the cultivar Zhonglü-1 was more tolerant to UV-B than the cultivar Qindou-20. Meanwhile, the cultivar Zhonglü-1 had lower CPD accumulation and susceptibility to CPD induction, higher photorepair capacity and same dark repair capacity as compared with the cultivar Qindou-20. Different UV-B sensitivities between two mung bean cultivars may be mainly caused by the differences in CPD accumulation, which are caused by the different susceptibility to CPD induction and the different photorepair capacities. In addition, the different susceptibility to CPD induction between two mung bean cultivars is related to the different levels of UV-absorbing compounds

  3. Synthesis of 2-substituted 9-oxa-guanines {5-aminooxazolo[5,4-d]pyrimidin-7(6H-ones} and 9-oxa-2-thio-xanthines {5-mercaptooxazolo[5,4-d]pyrimidin-7(6H-ones}

    2008-07-01

    Full Text Available Oxazolo[5,4-d]pyrimidines can be considered as 9-oxa-purine analogs of naturally occurring nucleic acid bases. Interest in this ring system has increased due to recent reports of biologically active derivatives. In particular, 5-aminooxazolo[5,4-d]pyrimidine-7(6H-ones (9-oxa-guanines have been shown to inhibit ricin. The preparation of a series of 2-substituted 5-aminooxazolo[5,4-d]pyrimidin-7(6H-ones and related 5-thio-oxazolo[5,4-d]pyrimidines is described, including analogs suitable for further elaboration employing “click” chemistry utilizing copper-catalyzed Huisgen 1,3-dipolar cycloadditions. Two of the compounds prepared were found to inhibit ricin with IC50 ca. 1–3 mM.

  4. Linerless label device and method

    Binladen, Abdulkari

    2016-01-14

    This apparatus and method for applying a linerless label to an end user product includes a device with a printer for printing on a face surface of a linerless label, and a release coat applicator for applying a release coat to the face surface of the label; another device including an unwinder unit (103) to unwind a roll of printed linerless label; a belt (108); a glue applicator (102) for applying glue to the belt; a nip roller (106) for contacting and applying pressure to the face surface of the linerless label such that the glue on the belt transfers to the back surface of the linerless label; at least one slitting knife 105) positioned downstream the belt and a rewinder unit (104) positioned downstream the slitting knife; and a third device which die cuts and applies the linerless label to an end user object.

  5. Label-Guided Graph Exploration with Adjustable Ratio of Labels

    Zhang, Meng; Tang, Jijun

    2012-01-01

    The graph exploration problem is to visit all the nodes of a connected graph by a mobile entity, e.g., a robot. The robot has no a priori knowledge of the topology of the graph or of its size. Cohen et al. \\cite{Ilcinkas08} introduced label guided graph exploration which allows the system designer to add short labels to the graph nodes in a preprocessing stage; these labels can guide the robot in the exploration of the graph. In this paper, we address the problem of adjustable 1-bit label guided graph exploration. We focus on the labeling schemes that not only enable a robot to explore the graph but also allow the system designer to adjust the ratio of the number of different labels. This flexibility is necessary when maintaining different labels may have different costs or when the ratio is pre-specified. We present 1-bit labeling (two colors, namely black and white) schemes for this problem along with a labeling algorithm for generating the required labels. Given an $n$-node graph and a rational number $\\rh...

  6. 6-(4-Amino-1-methyl-2-(methylthio-6-oxo-1,6-dihydro-pyrimidin-5-yl-3,6-dimethyl-2-(methylthio-6,7-dihydro-3H-pyrrolo[2,3-d]pyrimidine-4,5-dione

    Pablo E. Romo

    2015-02-01

    Full Text Available The title compound 6-(4-amino-1-methyl-2-(methylthio-6-oxo-1,6-dihydro-pyrimidin-5-yl-3,6-dimethyl-2-(methylthio-6,7-dihydro-3H-pyrrolo[2,3-d]pyrimidine-4,5- dione was synthesized in 60% yield by a microwave-induced cyclocondensation reaction of aminopyrimidine with pyruvic acid in the presence of cerium ammonium nitrate (CAN as catalyst.

  7. New Convenient Strategy for Annulation of Pyrimidines to Thiophenes or Furans via the One-pot Multistep Cascade Reaction of 1H-Tetrazoles with Aliphatic Amines.

    Pokhodylo, Nazariy T; Shyyka, Olga Ya; Matiychuk, Vasyl S; Obushak, Mykola D

    2015-07-13

    A versatile, convenient, efficient and high-yield synthetic method for 2-R(3),R(4)-amino-5-R(1)-6-R(2)-thieno[2,3-d]pyrimidin-4(3H)-ones, 2-R(3),R(4)-amino-5-R(1)-6-R(2)-thieno[3,2-d]pyrimidin-4(3H)-ones, and benzofuro[3,2-d]pyrimidin-4(3H)-ones preparation has been developed. The reaction proceeded without using solvents and included several steps. A variety of thieno[2,3-d]pyrimidine and thieno[3,2-d]pyrimidine derivatives with substituents of different nature were obtained in high yields from substituted alkyl 2-(1H-tetrazol-1-yl)thiophene-3-carboxylates, 3-(1H-tetrazol-1-yl)thiophene-2-carboxylates, and 3-(1H-tetrazol-1-yl)benzofuran-2-carboxylate after their treatment with aliphatic amines. PMID:26091557

  8. In vitro anti-Giardia lamblia activity of 2-aryl-3-hydroxymethyl imidazo[1,2-a]pyridines and -pyrimidines, individually and in combination with albendazole.

    Velázquez-Olvera, Stephanía; Salgado-Zamora, Héctor; Jiménez-Cardoso, Enedina; Campos-Aldrete, Maria-Elena; Pérez-González, Cuauhtémoc; Ben Hadda, Taibi

    2016-03-01

    Giardiasis is a major diarrheal disease found throughout the world, the causative agent being the flagellate protozoan Giardia intestinalis. Infection is more common in children than in adults. The appearance of drug resistance has complicated the treatment of several parasitic diseases, including giardiasis. Thus, the aim of this investigation was to make an in vitro evaluation of the antigiardia response of synthetic derivatives 2-aryl-3-hydroxymethylimidazo[1,2-a]pyridines 1 and -pyrimidines 2 against trophozoites of Giardia lamblia WB, in comparison with the reference drug, albendazole. Additionally, the synergistic action of albendazole in combination with each of the most active 2-aryl-3-hydroxymethyl imidazo[1,2-a]pyridines and pyrimidines was also assessed. Based on the IC50 values obtained, the best anti-Giardia activity was provided by the 3-hydroxymethyl-4-fluorophenylimidazo[1,2-a]pyrimidine derivative 2c and the corresponding imidazo[1,2-a]pyrimidine with the p-tolyl substituent 2d, followed by 2a and 2b. These four compounds showed effectiveness at a concentration similar to that of albendazole. Regarding synergism, the IC50 of the combination of albendazole with 2a, 2b or 2c gave the best anti-Giardia action, showing greater efficacy than albendazole alone. Hence, G. lamblia WB showed high susceptibility to some 2-aryl-3-hydroxymethyl imidazo[1,2-a] pyrimidines, which acted synergistically when used in combination with albendazole. PMID:26657313

  9. Labelled compounds. (Pt. B)

    Since the end of World War II there has been a tremendous increase in the number of compounds that have been synthesized with radioactive or stable isotopes. They have found application in many diverse fields, so much so, that hardly a single area in pure and applied science has not benefited. Not surprisingly it has been reflected in appearance of related publications. The early proceedings of the Symposia on Advances in Trace Methodology were soon followed by various Euratom sponsored meetings in which methods of preparing and storing labelled compounds featured prominently. In due course a resurgence of interest in stable isotopes, brought about by their greater availability (also lower cost) and partly by development of new techniques such as gas chromatography - mass spectrometry (gc-ms), led to the publication of proceedings of several successful conferences. More recently conferences dealing with the synthesis and applications of isotopes and isotopically labelled compounds have been established on a regular basis. In addition to the proceedings of conferences and journal publications individuals left their mark by producing definitive texts, usually on specific nuclides. Only the classic two volume publication of Murray and Williams (Organic syntheses with isotopes, New York 1985), now over 30 years old and out of print, attempted to do justice to several nuclides. With the large amount of work that has been undertaken since then it seems unlikely that an updated edition could be produced. The alternative strategy was to ask scientists currently active to review specific areas and this is the approach adopted in the present series of monographs. In this way it is intended to cover the broad advances that have been made in the synthesis and applications of isotopes and isotopically labelled compounds in the physical and biomedical sciences. (author). refs.; figs.; tabs

  10. Waisda?: video labeling game

    Hildebrand, Michiel; Brinkerink, M.; Gligorov, R.; Steenbergen, Van; Huijkman, J.; Oomen, J.

    2013-01-01

    The Waisda? video labeling game is a crowsourcing tool to collect user-generated metadata for video clips. It follows the paradigm of games-with-a-purpose, where two or more users play against each other by entering tags that describe the content of the video. Players score points by entering the same tags as one of the other players. As a result each video that is played in the game is annotated with tags that are anchored to a time point in the video. Waisda? has been deployed in two projec...

  11. From Label to Practice

    Byrkjeflot, Haldor; Strandgaard, Jesper; Svejenova, Silviya

    2013-01-01

    This article examines the process of creation of new Nordic cuisine (NNC) as a culinary innovation, focusing on the main stages, actors, and mechanisms that shaped the new label and its practices and facilitated its diffusion in the region and internationally. Fast-paced diffusion was possible...... because NNC was conceived as an identity movement, triggered by active involvement of entrepreneurial leaders from the culinary profession, high-profile political supporters, legitimating scientists, disseminating media, and interpreting audiences. It was facilitated by three mechanisms: First, the use of...

  12. Labeled bile acids

    A general short procedure for the introduction of 13C to the side chain of bile acids is described. Suitable (Z)-pregn-17(20)-enes are key intermediates, while the isotope is introduced by an ene reaction with [1,2,3-13C3]-methyl propiolate. For the labeling with tritium, the unlabeled product of the ene synthesis, a Δsup(5,16,22)-triene was saturated selectively at 16,17 and 22,23 with tritium gas. (author)

  13. A Food Labeling

    ... " ﻗﺎﻧﻮن اﻟﺒﻄﺎﻗﺎت واﻟﺘﻮﻋﻴﺔ اﻟﻐﺬاﺋﻴﺔ " [ Nutrition Labeling and Education Act ... ﻟﻠﻌﺼﻴﺮ اﻟﻤﻜﻮن ﺑﺈﺿﺎﻓﺔ اﻟﻤﺎء إﻟﻰ ﺧﻼﺻﺔ ﻣﺮآﺰة : ﻳﺠﺮى اﻟﺤﺴﺎب ﻣﻦ ﺟﺪول Brix ﻓﻲ 21 CFR 101.30(h)(1) ...

  14. Towards Multi Label Text Classification through Label Propagation

    Shweta C. Dharmadhikari

    2012-06-01

    Full Text Available Classifying text data has been an active area of research for a long time. Text document is multifaceted object and often inherently ambiguous by nature. Multi-label learning deals with such ambiguous object. Classification of such ambiguous text objects often makes task of classifier difficult while assigning relevant classes to input document. Traditional single label and multi class text classification paradigms cannot efficiently classify such multifaceted text corpus. Through our paper we are proposing a novel label propagation approach based on semi supervised learning for Multi Label Text Classification. Our proposed approach models the relationship between class labels and also effectively represents input text documents. We are using semi supervised learning technique for effective utilization of labeled and unlabeled data for classification. Our proposed approach promises better classification accuracy and handling of complexity and elaborated on the basis of standard datasets such as Enron, Slashdot and Bibtex.

  15. CNN: Single-label to Multi-label

    Wei, Yunchao; Xia, Wei; Huang, Junshi; Ni, Bingbing; Dong, Jian; Zhao, Yao; Yan, Shuicheng

    2014-01-01

    Convolutional Neural Network (CNN) has demonstrated promising performance in single-label image classification tasks. However, how CNN best copes with multi-label images still remains an open problem, mainly due to the complex underlying object layouts and insufficient multi-label training images. In this work, we propose a flexible deep CNN infrastructure, called Hypotheses-CNN-Pooling (HCP), where an arbitrary number of object segment hypotheses are taken as the inputs, then a shared CNN is...

  16. Label and Label-Free Detection Techniques for Protein Microarrays

    Amir Syahir

    2015-04-01

    Full Text Available Protein microarray technology has gone through numerous innovative developments in recent decades. In this review, we focus on the development of protein detection methods embedded in the technology. Early microarrays utilized useful chromophores and versatile biochemical techniques dominated by high-throughput illumination. Recently, the realization of label-free techniques has been greatly advanced by the combination of knowledge in material sciences, computational design and nanofabrication. These rapidly advancing techniques aim to provide data without the intervention of label molecules. Here, we present a brief overview of this remarkable innovation from the perspectives of label and label-free techniques in transducing nano‑biological events.

  17. Modeling the effects of labeling

    Juhl, Hans Jørn; Fjord, Thomas Ahle; Poulsen, Carsten Stig

    A new approach to evaluate the consequences of labeling is presented and applied to test the potential effect of a label on fresh fish. Labeling effects on quality perceptions and overall quality are studied. The empirical study is based on an experimental design and nearly 500 respondents partic...... participated in an in home test. The results indicate that catch time alone is not enough to work as an efficient predictor of actual perceived quality.......A new approach to evaluate the consequences of labeling is presented and applied to test the potential effect of a label on fresh fish. Labeling effects on quality perceptions and overall quality are studied. The empirical study is based on an experimental design and nearly 500 respondents...

  18. Edge colouring by total labellings

    Brandt, Stephan; Rautenbach, D.; Stiebitz, M.;

    2010-01-01

    We introduce the concept of an edge-colouring total k-labelling. This is a labelling of the vertices and the edges of a graph G with labels 1, 2, ..., k such that the weights of the edges define a proper edge colouring of G. Here the weight of an edge is the sum of its label and the labels of its...... two endvertices. We define χ (G) to be the smallest integer k for which G has an edge-colouring total k-labelling. This parameter has natural upper and lower bounds in terms of the maximum degree Δ of G : ⌈ (Δ + 1) / 2 ⌉ ≤ χ (G) ≤ Δ + 1. We improve the upper bound by 1 for every graph and prove χ (G...

  19. Interaction of monoclonal antibodies directed against bromodeoxyuridine with pyrimidine bases, nucleosides, and DNA

    Although antibodies directed against bromodeoxyuridine (BrdU) are being used in both clinical and basic research laboratories as tools to study and monitor DNA synthesis, little is known about the epitopes with which they react. Four monoclonal antibodies directed against BrdU were produced and were characterized to learn more about the epitopes on BrdU which are important for antibody recognition, to identify compounds other than BrdU which react with the antibodies and which might interfere with immunologic assays for BrdU, and to characterize the reaction of these antibodies with BrdU-containing DNA. By radioimmunoassays, the antibodies generally reacted well with 5-iododeoxyuridine, 5-fluorodeoxyuridine, and 5-nitrouracil. However, none of the antibodies reacted well with uridine - indicating that a substituent on uridine C5 was essential for antibody reactivity - or with 5-bromo or iodo-cytosine, indicating that the region around pyrimidine C4 is important for antibody recognition. Although the antibodies reacted with 5-halogen-substituted uracil bases, the antibodies reacted much better with the corresponding halogenated nucleosides, indicating that the sugar moiety was important for recognition. The presence of a triphosphate group of C'5 of BrdU (i.e., BrdUTP) did not detectably alter antibody recognition. S1 nuclease treatment of purified DNA suggested that all four monoclonal antibodies reacted exclusively with single-stranded regions of BrdU-containing DNA. Comparison of detecting DNA synthesis by [3H]TdR incorporation followed by autoradiography with that by BrdU incorporation followed by indirect immunofluorescence indicated that the latter technique was both an accurate and a sensitive measure of DNA synthesis

  20. Cyclobutane pyrimidine dimers photolyase from extremophilic microalga: Remarkable UVB resistance and efficient DNA damage repair

    Highlights: • Chlamydomonas sp. ICE-L photolyase gene PHR2 is first cloned and expressed in E. coli. • PHR2 complemented E. coli could efficiently survival from UV radiation. • Expressed PHR2 photolyase has distinct photo-reactivation activity in vitro. - Abstract: Bacteria living in the Antarctic region have developed several adaptive features for growth and survival under extreme conditions. Chlamydomonas sp. ICE-Lis well adapted to high levels of solar UV radiation. A putative photolyase was identified in the Chlamydomonas sp. ICE-L transcriptome. The complete cDNA sequence was obtained by RACE-PCR. This PHR encoding includes a polypeptide of 579 amino acids with clear photolyase signatures belonging to class II CPD-photolyases, sharing a high degree of homology with Chlamydomonas reinhardtii (68%). Real-time PCR was performed to investigate the potential DNA damage and responses following UVB exposure. CPD photolyase mRNA expression level increased over 50-fold in response to UVB radiation for 6 h. Using photolyase complementation assay, we demonstrated that DNA photolyase increased photo-repair more than 116-fold in Escherichia coli strain SY2 under 100 μw/cm2 UVB radiation. To determine whether photolyase is active in vitro, CPD photolyase was over-expressed. It was shown that pyrimidine dimers were split by the action of PHR2. This study reports the unique structure and high activity of the enzyme. These findings are relevant for further understanding of molecular mechanisms of photo-reactivation, and will accelerate the utilization of photolyase in the medical field

  1. Genetic and phylogenetic characterization of the type II cyclobutane pyrimidine dimer photolyases encoded by Leporipoxviruses

    Shope fibroma virus and myxoma virus encode proteins predicted to be Type II photolyases. These are enzymes that catalyze light-dependent repair of cyclobutane pyrimidine dimers (CPDs). When the Shope fibroma virus S127L gene was expressed in an Escherichia coli strain lacking functional CPD repair pathways, the expressed gene protected the bacteria from 70-75% of the ultraviolet (UV) light-induced cytotoxic DNA damage. This proportion suggests that Leporipoxvirus photolyases can only repair CPDs, which typically comprise ∼70% of the damage caused by short wavelength UV light. To test whether these enzymes can protect virus genomes from UV, we exposed virus suspensions to UV-C light followed by graded exposure to filtered visible light. Viruses encoding a deletion of the putative photolyase gene were unable to photoreactivate UV damage while this treatment again eliminated 70-90% of the lethal photoproducts in wild-type viruses. Western blotting detected photolyase protein in extracts prepared from purified virions and it can be deduced that the poxvirion interior must be fluid enough to permit diffusion of this ∼50-kDa DNA-binding protein to the sites where it catalyzes photoreactivation. Photolyase promoters are difficult to categorize using bioinformatics methods, as they do not obviously resemble any of the known poxvirus promoter motifs. By fusing the SFV promoter to DNA encoding a luciferase open reading frame, the photolyase promoter was found to exhibit very weak late promoter activity. These data show that the genomes of Leporipoxviruses, similar to that of fowlpox virus, encode catalytically active photolyases. Phylogenetic studies also confirmed the monophyletic origin of poxviruses and suggest an ancient origin for these genes and perhaps poxviruses

  2. Cyclobutane pyrimidine dimers photolyase from extremophilic microalga: Remarkable UVB resistance and efficient DNA damage repair

    Li, Chongjie [Key Laboratory of Marine Bioactive Substance, The First Institute of Oceanography, State Oceanic Administration, Qingdao 266061 (China); Ma, Li [Key Laboratory of Biofuels, and Shandong Provincial Key Laboratory of Energy Genetics, Qingdao Institute of Bioenergy and Bioprocess Technology, Chinese Academy of Sciences, Qingdao 266101 (China); Mou, Shanli [Yellow Sea Fisheries Research Institute, Chinese Academy of Fishery Sciences, Qingdao (China); Wang, Yibin, E-mail: wangyibin@fio.org.cn [Key Laboratory of Marine Bioactive Substance, The First Institute of Oceanography, State Oceanic Administration, Qingdao 266061 (China); Zheng, Zhou; Liu, Fangming; Qi, Xiaoqing; An, Meiling; Chen, Hao [Key Laboratory of Marine Bioactive Substance, The First Institute of Oceanography, State Oceanic Administration, Qingdao 266061 (China); Miao, Jinlai, E-mail: miaojinlai@163.com [Key Laboratory of Marine Bioactive Substance, The First Institute of Oceanography, State Oceanic Administration, Qingdao 266061 (China); State Key Laboratory of Biological Fermentation Engineering of Beer (In Preparation), Qingdao (China)

    2015-03-15

    Highlights: • Chlamydomonas sp. ICE-L photolyase gene PHR2 is first cloned and expressed in E. coli. • PHR2 complemented E. coli could efficiently survival from UV radiation. • Expressed PHR2 photolyase has distinct photo-reactivation activity in vitro. - Abstract: Bacteria living in the Antarctic region have developed several adaptive features for growth and survival under extreme conditions. Chlamydomonas sp. ICE-Lis well adapted to high levels of solar UV radiation. A putative photolyase was identified in the Chlamydomonas sp. ICE-L transcriptome. The complete cDNA sequence was obtained by RACE-PCR. This PHR encoding includes a polypeptide of 579 amino acids with clear photolyase signatures belonging to class II CPD-photolyases, sharing a high degree of homology with Chlamydomonas reinhardtii (68%). Real-time PCR was performed to investigate the potential DNA damage and responses following UVB exposure. CPD photolyase mRNA expression level increased over 50-fold in response to UVB radiation for 6 h. Using photolyase complementation assay, we demonstrated that DNA photolyase increased photo-repair more than 116-fold in Escherichia coli strain SY2 under 100 μw/cm{sup 2} UVB radiation. To determine whether photolyase is active in vitro, CPD photolyase was over-expressed. It was shown that pyrimidine dimers were split by the action of PHR2. This study reports the unique structure and high activity of the enzyme. These findings are relevant for further understanding of molecular mechanisms of photo-reactivation, and will accelerate the utilization of photolyase in the medical field.

  3. Structure, stability, and thermodynamics of a short intermolecular purine-purine-pyrimidine triple helix

    Pilch, D.S.; Shafer, R.H. (Univ. of California, San Francisco (United States)); Levenson, C. (Cetus Corp., Emeryville, CA (United States))

    1991-06-25

    The authors have investigated the structure and physical chemistry of the d(C{sub 3}T{sub 4}C{sub 3}){center dot}2(d(G{sub 3}A{sub 4}G{sub 3})) triple helix by polyacrylamide gel electrophoresis (PAGE), {sup 1}H NMR, and ultraviolet (UV) absorption spectroscopy. The triplex was stabilized with MgCl{sub 2} at neutral pH. PAGE studies verify the stoichiometry of the strands comprising the triplex and indicate that the orientation of the third strand in purine-purine-pyrimidine (pur-pur-pyr) triplexes is antiparallel with respect to the purine strand of the underlying duplex. Imino proton NMR spectra provide evidence for the existence of new purine-purine (pur{center dot}pur) hydrogen bonds, in addition to those of the Watson-Crick (W-C) base pairs, in the triplex structure. These new hydrogen bonds are likely to correspond to the interaction between third-strand guanine NH1 imino protons and the N7 atoms of guanine residues on the puring strand of the underlying duplex. Thermal denaturation of the triplex proceeds to single strands in one step, under the conditions used in this study. Binding of the third strand appears to enhance the thermal stability of the duplex by 1-3 C, depending on the DNA concentration. This marked enhancement in stability, coupled with the lack of an acidic pH requirement, suggests that pur-pur-pyr triplexes are appealing choices for use in applications involving oligonucleotide targeting of duplex DNA in vitro and in vivo.

  4. Structure, stability, and thermodynamics of a short intermolecular purine-purine-pyrimidine triple helix

    The authors have investigated the structure and physical chemistry of the d(C3T4C3)·2[d(G3A4G3)] triple helix by polyacrylamide gel electrophoresis (PAGE), 1H NMR, and ultraviolet (UV) absorption spectroscopy. The triplex was stabilized with MgCl2 at neutral pH. PAGE studies verify the stoichiometry of the strands comprising the triplex and indicate that the orientation of the third strand in purine-purine-pyrimidine (pur-pur-pyr) triplexes is antiparallel with respect to the purine strand of the underlying duplex. Imino proton NMR spectra provide evidence for the existence of new purine-purine (pur·pur) hydrogen bonds, in addition to those of the Watson-Crick (W-C) base pairs, in the triplex structure. These new hydrogen bonds are likely to correspond to the interaction between third-strand guanine NH1 imino protons and the N7 atoms of guanine residues on the puring strand of the underlying duplex. Thermal denaturation of the triplex proceeds to single strands in one step, under the conditions used in this study. Binding of the third strand appears to enhance the thermal stability of the duplex by 1-3 C, depending on the DNA concentration. This marked enhancement in stability, coupled with the lack of an acidic pH requirement, suggests that pur-pur-pyr triplexes are appealing choices for use in applications involving oligonucleotide targeting of duplex DNA in vitro and in vivo

  5. Comparative studies on the correlation between pyrimidine dimer formation and tyrosinase activity in Cloudman S91 melanoma cells after ultraviolet-irradiation

    The authors compared the induction of pyrimidine dimer densities after UV-irradiation in mouse melanoma cells before and after treatment with cholera toxin. Treatment with cholera toxin stimulated tyrosinase activity up to 50-fold, leading to a marked, visually apparent increase in cellular melanin concentrations. Results indicate that de novo melanin pigmentation induced via the c-AMP pathway is not involved in protection against UV-induced thymine-containing pyrimidine dimers. In separate experiments, irradiation of toxin-treated and untreated mouse melanoma cells with UVC or UVB light produced a 20-30% lower dimer density compared to irradiated human skin fibroblasts. This finding suggests that melanin has some protection properties against UV-induced pyrimidine dimers, although the exact defense mechanism seems highly complex. (author)

  6. In vivo excision of pyrimidine dimers is mediated by a DNA N-glycosylase in Micrococcus luteus but not in human fibroblasts

    It has been previously shown that Micrococcus luteus possesses a pyrimidine dimer-specific endonuclease which in vitro, functions as both an endonuclease and DNA-glycosylase. To determine if these combined activities function in vivo, the excision products of UV-irradiated M. luteus were isolated and examined. In addition, a procedure was devised to isolate and examine the excision products from UV-irradiated human fibroblasts to determine if an endonuclease/glycosylase activity functions in the excision of UV-induced pyrimidine dimers in human fibroblasts. It was shown that, in vivo, an endonuclease/glycosylase mechanism is utilized extensively in the repair of pyrimidine dimers by M. luteus, but that human fibroblasts do not appear to use this mechanism. (author)

  7. 2, 4-Diamino-6- hydroxy pyrimidine inhibits NSAIDs induced nitrosyl-complex EPR signals and ulcer in rat jejunum

    Bjarnason I

    2002-04-01

    Full Text Available Abstract Background It has been suggested that one aspect of non-steroidal anti-inflammatory drugs induced intestinal damage is due to either uncoupling of mitochondrial oxidative phosphorylation or inhibition of electron transport. We investigated the latter possibility using electron paramagnetic resonance spectroscopy. Results Electron paramagnetic studies of NSAIDS on sub-mitochondrial particles revealed that indomethacin, but not with nabumetone, bound to a site near to Complex I and ubiquinone to generate a radical species. Normal rats exhibited prominent [3Fe-4S]ox signals (g ~ 2.01 at 20 K. One hour after indomethacin there was a prominent, intense and broad absorption pattern at (g ~2.07 suggesting, appearance of radical species overlapping [3Fe-4S]ox and was unaffected by pretreatment with 2,4 diamino -6-hydroxy pyrimidine. At 24 hrs, when macroscopic ulcers were seen, there was a new signal due to a nitric oxide radical (NO•. In contrast, nabumetone and 2,4 diamino-6-hydroxy pyrimidine pre-treated animals receiving indomethacin exhibited electron paramagnetic resonance spectra identical to those of controls at 24 hrs and neither was associated with small intestinal ulcers. Indomethacin and 2,4 diamino hydroxy pyrimidine pre-treated rats, but not nabumetone, had increased intestinal permeability. Conclusion The results suggest that the in vivo effects of indomethacin modulate the mitochondrial respiratory chain directly at 1 h and 24 h through formation of nitric oxide. NO• appears to play an important role in the late pathogenic stages of NSAID enteropathy and may be the site for targeted treatment to reduce their toxicity.

  8. Infrared study of some 2-substituted-6-hydroxy-4-pyrimidine carboxylic acids. Correlation with MO-calculations

    IVAN O. JURANIC

    2000-06-01

    Full Text Available The IR spectra of a series of 2-substituted-6-hydroxy-4-pyrimidine carboxylic acids (substituent = OH, SH, CH3, CH3S and NH2 were studied from the aspect of the influence of the subsitutent on the polarizability of some bonds, keto-enol tautomerism and hydrogen bond formation. The spectra were taken using solids due to the low solubility of the acids. Theoretical calculations were done using the MNDO-AM1 semiempirical molecular-orbital method. The stabilities of various tautomers were calculated simulating the dielectric continuum using the COSMO facility of the MOPAC program package. Theoretical calculations were made for all the possible tautomers of the 2-substituted-6-hydroxy-4-pyrimidine carboxylic acids. For the most stable isomers, the vibrational spectra were calculated. For the majority of the compounds the most stable isomer was identified having the structure 2-Y-6-oxo-4-carboxy-3H-pyrimidine. Besides this structure, for the 2-amino-, and 2-methyl- derivatives the zwitterionic forms have very similar stability. The 2-hydroxy compound is most stable as the 2,6-dioxo-1H, 3H isomer. The calculated vibrations for the compounds with a single stable structure correlate very well with the experimental frequencies. For the 2-methyl- and 2-amino- compounds the correlation is considerably less satisfactory. The most probable reason for this deviation is the existence of two or more tautomets in equilibrium. The correlation of the measured frequencies and the pKa values of the acids, indicate that the same tautomers exist in the solid state and in the solution.

  9. Chemical modification of triplex-forming oligonucleotide to promote pyrimidine motif triplex formation at physiological pH.

    Torigoe, Hidetaka; Nakagawa, Osamu; Imanishi, Takeshi; Obika, Satoshi; Sasaki, Kiyomi

    2012-04-01

    Extreme instability of pyrimidine motif triplex DNA at physiological pH severely limits its use in wide variety of potential applications, such as artificial regulation of gene expression, mapping of genomic DNA, and gene-targeted mutagenesis in vivo. Stabilization of pyrimidine motif triplex at physiological pH is, therefore, crucial for improving its potential in various triplex-formation-based strategies in vivo. To this end, we investigated the effect of 3'-amino-2'-O,4'-C-methylene bridged nucleic acid modification of triplex-forming oligonucleotide (TFO), in which 2'-O and 4'-C of the sugar moiety were bridged with the methylene chain and 3'-O was replaced by 3'-NH, on pyrimidine motif triplex formation at physiological pH. The modification not only significantly increased the thermal stability of the triplex but also increased the binding constant of triplex formation about 15-fold. The increased magnitude of the binding constant was not significantly changed when the number and position of the modification in TFO changed. The consideration of the observed thermodynamic parameters suggested that the increased rigidity of the modified TFO in the free state resulting from the bridging of different positions of the sugar moiety with an alkyl chain and the increased hydration of the modified TFO in the free state caused by the introduction of polar nitrogen atoms may significantly increase the binding constant at physiological pH. The study on the TFO viability in human serum showed that the modification significantly increased the resistance of TFO against nuclease degradation. This study presents an effective approach for designing novel chemically modified TFOs with higher binding affinity of triplex formation at physiological pH and higher nuclease resistance under physiological condition, which may eventually lead to progress in various triplex-formation-based strategies in vivo. PMID:22245184

  10. Involvement and non-involvement of pyrimidine dimer formation in UV-B effects on Sorghum bicolor Moench seedlings

    In plants ultraviolet B (UV-B) radiation causes not only DNA lesion and other deleterious effects, but also assumingly contributes to normal photomorphogenesis mediated by a putative UV-B photoreceptor (s). In order to examine which UV-B effects do or do not involve DNA lesion, cyclobutane pyrimidine dimers (CPDs), thymine dimer (CTD), and pyrimidine (6-4) pyrimidinone photoproducts (6-4 PP) were determined by enzyme-linked immunosorbent assay or radioimmunoassay with regard to UV-B-induced anthocyanin synthesis and inhibition as well as coil formation (abnormal growth) of the first internode of Sorghum bicolor Moench. For anthocyanin, dark-grown 3-day-old seedlings were irradiated at various fluences with each of the three UV radiations having bands of (A) 295-345, (B) 300-350, and (C) 325-385 nm at !4 peak height, followed by far-red light (FR) to exclude phytochrome actions. For coil formation, a radiation similar to A was used. The variation of CPD level versus the wavelengths and fluences of UV-B did not correlate with that of anthocyanin synthesis, but did so with the inhibition of anthocyanin synthesis above a critical level of CPDs. Coil formation was also correlated with CPDs (measured as CTD) above a critical level, which was observed not only when CPD level was raised by increasing the fluence of UV-B, but also when it was lowered by UV-A photorepair. The results supported the view that anthocyanin induction does not involve DNA damage, whereas anthocyanin inhibition may be associated with it. The coil formation was indicated to be caused by it. Pyrimidine (6-4) pyrimidinone photoproducts were formed in proportion to CPDs, and hence, it was impossible to determine which of the two kinds of dimers was responsible. The presence of a fast elimination of CPDs (half-life of ca. 30 min) in the dark was suggested. (author)

  11. Aggregating Labels in Crowdsourcing Data

    Priisalu, Maria; Grey, Francois; Segal, Ben

    2015-01-01

    Project Specification Crowdsourcing is gaining popularity in academia with the launch of crowdsourcing platforms such as Crowdcrafting [Lombraña, 2015] and GeoTagX [UNOSAT, 2015]. There have been a number of proposed algorithms for the aggregation of true labels and a confusion matrix from crowdsourced labels for ordinal, nominal and binary labels. The work here consists of an implementation of the Dawid Skene [Dawid 1979] adaptation of the Expectation Maximization algorithm [D...

  12. Classification and Labelling for Biocides

    Rubbiani, Maristella

    2015-01-01

    CLP and biocides The EU Regulation (EC) No 1272/2008 on Classification, Labelling and Packaging of Substances and Mixtures, the CLP-Regulation, entered into force on 20th January, 2009. Since 1st December, 2010 the classification, labelling and packaging of substances has to comply with this Regulation. For mixtures, the rules of this Regulation are mandatory from 1st June, 2015; this means that until this date classification, labelling and packaging could either be carried out according to D...

  13. Co-Labeling for Multi-View Weakly Labeled Learning.

    Xu, Xinxing; Li, Wen; Xu, Dong; Tsang, Ivor W

    2016-06-01

    It is often expensive and time consuming to collect labeled training samples in many real-world applications. To reduce human effort on annotating training samples, many machine learning techniques (e.g., semi-supervised learning (SSL), multi-instance learning (MIL), etc.) have been studied to exploit weakly labeled training samples. Meanwhile, when the training data is represented with multiple types of features, many multi-view learning methods have shown that classifiers trained on different views can help each other to better utilize the unlabeled training samples for the SSL task. In this paper, we study a new learning problem called multi-view weakly labeled learning, in which we aim to develop a unified approach to learn robust classifiers by effectively utilizing different types of weakly labeled multi-view data from a broad range of tasks including SSL, MIL and relative outlier detection (ROD). We propose an effective approach called co-labeling to solve the multi-view weakly labeled learning problem. Specifically, we model the learning problem on each view as a weakly labeled learning problem, which aims to learn an optimal classifier from a set of pseudo-label vectors generated by using the classifiers trained from other views. Unlike traditional co-training approaches using a single pseudo-label vector for training each classifier, our co-labeling approach explores different strategies to utilize the predictions from different views, biases and iterations for generating the pseudo-label vectors, making our approach more robust for real-world applications. Moreover, to further improve the weakly labeled learning on each view, we also exploit the inherent group structure in the pseudo-label vectors generated from different strategies, which leads to a new multi-layer multiple kernel learning problem. Promising results for text-based image retrieval on the NUS-WIDE dataset as well as news classification and text categorization on several real-world multi

  14. Perturbation of maintenance and de novo DNA methylation in vitro by UVB (280-340 nm)-induced pyrimidine photodimers.

    Becker, F F; Holton, P.; Ruchirawat, M; Lapeyre, J N

    1985-01-01

    The effect of pyrimidine photodimers on transmethylation reactions catalyzed by a highly purified rat liver DNA (cytosine-5-)-methyltransferase (EC 2.1.1.37) that exhibits maintenance and de novo methylation activities was studied in vitro, using the viral substrates M13 mp9 replicative form (RF) DNA and the hemimethylated analog formed from primed synthesis of phage DNA in the presence of 2'-deoxy-5-methylcytidine 5'-triphosphate. These DNAs were irradiated with UVB (280-340 nm) at 900-3600 ...

  15. den V gene of bacteriophage T4 determines a DNA glycosylase specific for pyrimidine dimers in DNA.

    Seawell, P C; Smith, C A; Ganesan, A K

    1980-01-01

    Endonuclease V of bacteriophage T4 has been described as an enzyme, coded for by the denV gene, that incises UV-irradiated DNA. It has recently been proposed that incision of irradiated DNA by this enzyme and the analogous "correndonucleases" I and II of Micrococcus luteus requires the sequential action of a pyrimidine dimer-specific DNA glycosylase and an apyrimidinic/apurinic endonuclease. In support of this two-step mechanism, we found that our preparations of T4 endonuclease V contained a...

  16. Prodrugs of purine and pyrimidine analogues for the intestinal di/tri-peptide transporter PepT1

    Thomsen, Anne Engelbrecht; Friedrichsen, Gerda Marie; Sørensen, Arne Hagsten; Andersen, Rikke; Nielsen, Carsten Uhd; Brodin, Birger; Begtrup, Mikael; Frokjaer, Sven; Steffansen, Bente

    A general drug delivery approach for increasing oral bioavailability of purine and pyrimidine analogues such as acyclovir may be to link these compounds reversibly to stabilized dipeptide pro-moieties with affinity for the human intestinal di/tri-peptide transporter, hPepT1. In the present study......, novel L-Glu-Sar and D-Glu-Ala ester prodrugs of acyclovir and 1-(2-hydroxyethyl)-linked thymine were synthesized and their affinities for hPepT1 in Caco-2 cells were determined. Furthermore, the degradation of the prodrugs was investigated in various aqueous and biological media and compared to the...

  17. Cleaner and convenient preparation of 3-(4,6-dimethoxy-pyrimidin-2-yloxy)-2-methyl-phenol

    文岳中; 方兆华; 刘维屏

    2004-01-01

    Environmental concerns have highlighted the need of cleaner technologies. A cleaner, convenient and selectivetechnology has been developed for the preparation of 3-(4,6-dimethoxy-pyrimidin-2-yloxy)-2-methyl-phenol (DPMP) from2-methyl-benzene-l,3-diol in water as solvent. The isolated yield of DPMP is up to 86% in good selectivity. The productstructure was characterized by conventional methods, 1H-NMR and MS. This technology belongs to the modern concept ofenvironmentally friendly low wastes or non-wastes technology (LWNWT).

  18. Study on Inhibitors of Methionine Synthase Ⅷ: Synthesis of 2,5-Diamino-4-oxo-6- (3-butenyl) pyrimidine

    ZHANG Zhi-Li; WANG Hong-Tao; WANG Xiao-Wei; MA Xiao-Yan; LIU Jun-Yi; R.J. Griff; B.T. Golding

    2003-01-01

    @@ Cobalamin-dependent methionine synthase plays a crucial role in folate metabolism and such would appear to be an excellent target for rational antifolate drug design. However, to date, no anticancer agents directed at this enzyme are available, but the enzyme is efficiently and specifically inhibited by N2O and this has proven invaluable for evaluating the biochemical consequence of enzyme inhibition and for mechanistic studies. [1,2] 2,5-Diamino-4-oxo-6-(3-butenyl) pyrimidine, a key intermediate in synthetic inhibitors of methionine synthase, was first synthesized using γbutenyl-β-ketoester and guanidine carbonate (Scheme 1). [3

  19. Infrared study of some 2-substituted-6-hydroxy-4-pyrimidine carboxylic acids. Correlation with MO-calculations

    Juranic, Ivan O.; BRATISLAV Z. JOVANOVIC; UBAVKA B. MIOC; LJUBINKA J. BOGUNOVIC

    2000-01-01

    The IR spectra of a series of 2-substituted-6-hydroxy-4-pyrimidine carboxylic acids (substituent = OH, SH, CH3, CH3S and NH2) were studied from the aspect of the influence of the subsitutent on the polarizability of some bonds, keto-enol tautomerism and hydrogen bond formation. The spectra were taken using solids due to the low solubility of the acids. Theoretical calculations were done using the MNDO-AM1 semiempirical molecular-orbital method. The stabilities of various tautomers were calcul...

  20. Development of a series of aryl pyrimidine kynurenine monooxygenase inhibitors as potential therapeutic agents for the treatment of Huntington's disease.

    Toledo-Sherman, Leticia M; Prime, Michael E; Mrzljak, Ladislav; Beconi, Maria G; Beresford, Alan; Brookfield, Frederick A; Brown, Christopher J; Cardaun, Isabell; Courtney, Stephen M; Dijkman, Ulrike; Hamelin-Flegg, Estelle; Johnson, Peter D; Kempf, Valerie; Lyons, Kathy; Matthews, Kimberly; Mitchell, William L; O'Connell, Catherine; Pena, Paula; Powell, Kendall; Rassoulpour, Arash; Reed, Laura; Reindl, Wolfgang; Selvaratnam, Suganathan; Friley, Weslyn Ward; Weddell, Derek A; Went, Naomi E; Wheelan, Patricia; Winkler, Christin; Winkler, Dirk; Wityak, John; Yarnold, Christopher J; Yates, Dawn; Munoz-Sanjuan, Ignacio; Dominguez, Celia

    2015-02-12

    We report on the development of a series of pyrimidine carboxylic acids that are potent and selective inhibitors of kynurenine monooxygenase and competitive for kynurenine. We describe the SAR for this novel series and report on their inhibition of KMO activity in biochemical and cellular assays and their selectivity against other kynurenine pathway enzymes. We describe the optimization process that led to the identification of a program lead compound with a suitable ADME/PK profile for therapeutic development. We demonstrate that systemic inhibition of KMO in vivo with this lead compound provides pharmacodynamic evidence for modulation of kynurenine pathway metabolites both in the periphery and in the central nervous system. PMID:25590515

  1. Labelled molecules, modern research implements

    Details of the synthesis of carbon 14- and tritium-labelled molecules are examined. Although the methods used are those of classical organic chemistry the preparation of carbon 14-labelled molecules differs in some respects, most noticeably in the use of 14CO2 which requires very special handling techniques. For the tritium labelling of organic molecules the methods are somewhat different, very often involving exchange reactions. The following are described in turn: the so-called Wilzbach exchange method; exchange by catalysis in solution; catalytic hydrogenation with tritium; reductions with borotritides. Some applications of labelled molecules in organic chemistry, biochemistry and pharmacology are listed

  2. The radioactive labeling of monocytes

    With the aim of studying a possible relationship between circulating monocytes and Sternberg-Reed cells investigations were started on the specific labeling of monocytes. In this thesis the literature on the pertinent data has been reviewed and a series of experiments on the monocyte labeling procedure has been described. The principles of cell labeling with radioactive compounds were discussed. 1. Total separation of the particular cell population to be labeled and subsequent labeling with a non-specific radiopharmaceutical. 2. Specific cell labeling in a mixture of cell types based on a well defined affinity of the cell under study for the radiopharmaceutical used. Next the radionuclides that can be used for cell labeling purposes were discussed with special attention for 111In and its chelates. The principles of radiodosimetry were also discussed shortly. This section was focussed on the radiation dose the labeled cells receive because of the intracellular localized radioactivity. The radiation burden is high in comparison to amounts of radiation known to affect cell viability. A newly developed method for labeling monocytes specifically by phagocytosis of 111In-Fe-colloid without apparent loss of cells was described in detail. (Auth.)

  3. 76 FR 75809 - Prior Label Approval System: Generic Label Approval

    2011-12-05

    ... the type of packaging material on which the label is printed; n. Brand name changes, provided that... poultry products will take effect January 1, 2012 (75 FR 82148, Dec. 29, 2010). These mandatory features..., location, and indication of final color. To obtain sketch label approval, domestic meat and...

  4. Laser labeling, a safe technology to label produce

    Laser labeling of fruits and vegetables is an alternative means to label produce. Low energy CO2 laser beams etch the surface showing the contrasting underlying layer. These etched surfaces can promote water loss and potentially allow for entry of decay organisms. The long-term effects of laser labe...

  5. Heteroarylether 1,3-diarylureas in the thieno[3,2-d]pyrimidine series as VEGFR2 tyrosine kinase inhibitors : synthesis, docking studies, enzymatic and cellular assays

    Queiroz, Maria João R. P.; Peixoto, Daniela; Soares, Pedro; Abreu, Rui M. V.; Froufe, Hugo J. C.; Ricardo C. Calhelha; Ferreira, Isabel C. F. R.; Costa, Raquel; Soares, Raquel

    2013-01-01

    A number of thienopyrimidines derivatives have shown potent YEGFR2 (Vascular Endothelium Growth Factor Receptor2) inhibition activity [ 1]. YEGF is a surrogate marker of angiogenesis that activates VEGFR2 in endothelial cells. VEGF induces proliferation, migration and anastomosis of these cells. Here we present the synthesis of new l-aryl-3-[4-(thieno[3,2-d]pyrimidin-4-yloxy)phenyl]ureas, by reaction of 4-aminophenol with 4-chlorothieno[3,2-d]pyrimidine giving compound 1, which wa...

  6. Synthesis and Antimicrobial Activity of Some New Thiadiazoles, Thioamides, 5-Arylazothiazoles and Pyrimido[4,5-d][1,2,4]triazolo[4,3-a]pyrimidines

    Abdou O. Abdelhamid

    2016-08-01

    Full Text Available A novel series of 1,3,4-thiadiazoles, 5-arylazothiazoles and hexahydropyrimido-[4,5-d][1,2,4]triazolo[4,3-a]pyrimidines were synthesized via reaction of hydrazonoyl halides with each of alkyl carbothioates, carbothioamides and 7-thioxo-5,6,7,8-tetrahydropyrimido-[4,5-d]pyrimidine-2,4(1H,3H-diones in the presence of triethylamine. The structures of the newly synthesized compounds were established based on their spectral data, elemental analyses and alternative synthetic routes whenever possible. Also, the newly synthesized compounds were screened for their antimicrobial activity against various microorganisms.

  7. An efficient synthesis of novel pyrano[2,3-d]- and furopyrano[2,3-d]pyrimidines via indium-catalyzed multi-component domino reaction

    Gohain Mukut

    2006-06-01

    Full Text Available Abstract Various novel pyrano [2,3-d]pyrimidines 5 and furopyrano [2,3-d]pyrimidines 7 were synthesized in 80–99% yields via a multicomponent domino Knoevenagel/hetero-Diels-Alder reaction of 1,3-dimethyl barbituric acid with an aromatic aldehyde and ethyl vinyl ether/2,3-dihydrofuran in presence of 1 mol% of indium(III chloride. The reaction also proceeds in aqueous media without using any catalyst, but the yield is comparatively less (65–70%.

  8. Design, Synthesis and Pharmacological Evaluation of New Nonsteroidal Anti-Inflammatory Derived from 3-Aminobenzothieno[2,3-d]pyrimidines

    Hend Nagah Hafez; Omar Khalid Al-Duaij; Abdel-Rhman Barakat A. El-Gazzar

    2013-01-01

    During the last few years, condensed thienopyrimidine derivatives have received considerable attention. The therapeutic importance of thienopyrimidines prompted us to synthesize some of spiro(benzothieno[2,3-d]pyrimidine-4-one) derivatives. Some of the novel benzothino-pyrimidine derivatives 3a, 9b, 10b, 11a, 11b, and 11c showed considerable potent anti-inflammatory and analgesic activity of superior G.I.T. safety profile in experimental rats in comparing to indomethacin and tramadol as refe...

  9. Poly[bis­(methanol-κO)tris­(μ-pyrimidine-κ2 N:N′)tetra­kis(thio­cyanato-κN)dinickel(II)

    Mario Wriedt; Sina Sellmer; Inke Jess; Christian Näther

    2009-01-01

    In the crystal structure of the title compound, [Ni2(NCS)4(C4H4N2)3(CH3OH)2]n, each nickel(II) cation is coordinated by three N-bonded pyrimidine ligands, two N-bonded thiocyanate anions and one O-bonded methanol molecule in a distorted octahedral environment. The asymmetric unit consists of one nickel cation, two thiocyanate anions and one methanol molecule in general positions, as well as one pyrimidine ligand located around a twofold rotation axis. The crystal structure consists of ...

  10. One-pot synthesis of pyrido[2,3-d]pyrimidine derivatives using sulfonic acid functionalized SBA-15 and the study on their antimicrobial activities

    Ghodsi Mohammadi Ziarani

    2015-11-01

    Full Text Available A simple and clean one-pot method for the preparation of 7-amino-2,4-dioxo-5-aryl-1,2,3,4-tetrahydropyrido[2,3-d]pyrimidine-6-carbonitrile derivatives using 6-amino uracil, various aromatic aldehydes and malononitrile in the presence of sulfonic acid functionalized SBA-15 (SBA-Pr-SO3H is described. Some of synthesized pyrido[2,3-d]pyrimidines showed antimicrobial activities against some fungi and gram positive and negative bacteria.

  11. Discovery of Substituted Hydroxylphenyl Pyrimidine-2(1H) Thione as a New Series of Antioxidant using AAU and AAI Method

    Dudhe, Rupesh; Sharma, Pramod Kumar; Prabhaker Kumar VERMA

    2014-01-01

    A series of substituted pyrimidine has been discovered as a new class of potent antioxidant. 6-(Substituted aldehyde)- 3,4-dihydro-1-(tetrahydro-3,4-dihydroxy-5-hydroxymethyl)furan-2-yl)-4-(4-hydroxyphenyl)pyrimidine-2(1H)-thione derivative (XVII-XXIV) was synthesized from the 6-(Substituted aldehyde) -4-phenylpyrimidine-2(1H)-thione derivative (IX-XVI) through the reaction mechanisms of Claisen-Schmidt, Cyclization and Satos fusion. The structures of the synthesized compounds were elucidated...

  12. Oxygen labelled CO2

    Tests were carried out as to whether additional information concerning pulmonary gas exchange could be obtained from the application of oxygen labelled carbon dioxide. Single breath experiments were performed on two healthy subjects with 0.1 percent C16O18O and 2.8 percent C18O2 in the inspiratory gas. Breath-hold time was varied between 0.5-20s in different experiments. The 18O-concentration of the end-expired gas bi-exponentially decreased with increasing breath-hold time. The high and low rate constants 4s-1 and 0.12s-1 for C18O2 and 2.5s-1 and 0.87s-1 for C16O18O were derived, respectively. These results, together with model calculations, suggest: 1) the rapid disappearance of C18O2 from the alveolar space is primarily limited by diffusion, so that this isotopic species can be applied to quantify pulmonary diffusing conditions; 2) the lower disappearance rate of C16O18O is caused by a lower equilibration kinetics in blood, so that this isotopic species offers a possibility to study carbonic anhydrase activity of the red cells in vivo; 3) the slow phase of label decay is influenced by both alveolar dead space and carbonic anhydrase activity of the pulmonary tissues. Pathological dead spaces are expected to be sensitively detectable by C16O18O as well as by C18O2. (author). 4 refs.; 4 figs

  13. Meat and Poultry Labeling Terms

    ... Food Standards and Labels: The Facts Labeling and Marketing Information [ Top of Page ] OVEN PREPARED: Product is fully cooked and ready to eat. [ Top of Page ] YOUNG TURKEY: Turkeys of either sex that are less than 8 months of age according to present regulations. [ Top of Page ] Last ...

  14. Nutrition Marketing on Food Labels

    Colby, Sarah E.; Johnson, LuAnn; Scheett, Angela; Hoverson, Bonita

    2010-01-01

    Objective: This research sought to determine how often nutrition marketing is used on labels of foods that are high in saturated fat, sodium, and/or sugar. Design and Setting: All items packaged with food labels (N = 56,900) in all 6 grocery stores in Grand Forks, ND were surveyed. Main Outcome Measure(s): Marketing strategy, nutrient label…

  15. Part-1: Design, synthesis and biological evaluation of novel bromo-pyrimidine analogs as tyrosine kinase inhibitors.

    Munikrishnappa, Chandrashekar Suradhenupura; Puranik, Sangamesh B; Kumar, G V Suresh; Prasad, Y Rajendra

    2016-08-25

    A novel series of 5-bromo-pyrimidine derivatives (5a-l, 6a-h, 9a-m and 10a-d) were synthesized through multi step reactions starting from 5-bromo-2,4-dichloro pyrimidine. The newly synthesized compounds were characterized using elemental analysis and spectral data (IR, (1)H NMR, (13)C NMR and LC-MS) analysis. The titled compounds were evaluated for their in vitro cytotoxic activity against tumor cell lines panel consisted of HCT116 (human colon cancer cell line), A549 (human lung cancer cell line), K562 (human chronic myeloid leukemia cell line), U937 (human acute monocytic myeloid leukemia cell line), and L02 (human normal cell line) by using MTT assay Mosmann's method. As most of the compounds are highly potent against K562 cells, all the synthesized compounds were evaluated for Bcr/Abl tyrosine kinase inhibitory activity by using well-established ADP-Glo assay method. Dasatinib was utilized as positive control to validate in both biological evaluations. The biological activity revealed that the compounds 5c, 5e, 6g, 9e, 9f and 10c were potent Bcr/Abl kinase inhibitors among the titled compounds. Thus these compounds may be promising lead compounds to be developed as an alternative for current Dasatinib therapy. PMID:27155464

  16. Morpholino, piperidino, and pyrrolidino derivatives of pyrimidine nucleosides as inhibitors of ribonuclease A: synthesis, biochemical, and crystallographic evaluation.

    Samanta, Anirban; Leonidas, Demetres D; Dasgupta, Swagata; Pathak, Tanmaya; Zographos, Spyros E; Oikonomakos, Nikos G

    2009-02-26

    Six 5'-deoxy-5'-morpholine, piperidine, and pyrrolidine of pyrimidine nucleosides have been synthesized and characterized. Their inhibitory action to ribonuclease A has been studied by biochemical analysis and X-ray crystallography. These compounds are moderate inhibitors of RNase A with mid-to-upper micromolar inhibition constants (K(i)). The high resolution X-ray crystal structures of the RNase A-inhibitor complexes have shown that all inhibitors bind at the enzyme catalytic cleft with the pyrimidine nucleobase at the B(1)R(2) subsites while the 5' group binds away from the main subsite P(1), where P-O(5') bond cleavage occurs, toward the solvent close to subsite P(0). Structure-activity relationship analysis has demonstrated that the compounds with the larger group in the 5' position are more potent. Comparative structural analysis of these RNase A complexes with other similar RNase A-ligand complexes provides a structural explanation of their potency and suggests ways to improve their efficiency and selectivity. These inhibitors can be the starting point for the development of compounds that can be used as pharmaceuticals against pathologies associated with RNase A homologues such as human angiogenin, which is implicated in tumor induced neovascularization. PMID:19173562

  17. Unscheduled DNA synthesis: a quantitative indicator of residual immunodetectable pyrimidine dimers in human fibroblasts after ultraviolet-B irradiation

    The authors studied the use of the rate of unscheduled DNA synthesis (UDS) as an indicator of UV-B induced DNA damage. Human fibroblasts were irradiated with UV radiation at 290, 313 or 365 nm. The LD50 was 85 J/m2 at 290 nm, 4500 J/m2 as 313 nm, and 70 kJ/m2 at 365 nm. Analysis of UDS measurements indicated complete arrest of repair processes within 24 h after irradiation, irrespective of dose (in the range 10-60 J/m2 at 290 nm, and 250-1000 J/m2 at 313 nm). Irradiation at 365 nm failed to yield detectable evidence of UDS. Incubation of irradiated cells with an antiserum directed against both 6-4 type and cyclobutane-type pyrimidine dimers shows a clear parallelism between disappearance of antibody-binding determinants and variation of the rate of UDS vs time after the end of irradiation. It is concluded that in UV-B irradiated normal cultured human fibroblasts, lack of UDS reflects absence of immunodetectable pyrimidine dimers. (author)

  18. Cyclobutane-type pyrimidine photodimer formation and induction of ornithine decarboxylase in human skin fibroblasts after UV irradiation

    Cyclobutane-type pyrimidine photodimers as well as the induction of ornithine decarboxylase (ODC) may serve as biochemical markers of the mutagenic and carcinogenic effects of ultraviolet light (UV). For this reason, it is important to compare the formation of pyrimidine dimers with the induction of ODC in human skin fibroblasts after irradiation with UVC (200-290 nm) and UVB (290-320 nm). In our studies we determined cytosine-thymine (C-T) as well as thymine-thymine dimer yields (T-T) by high-pressure liquid chromatography in cultures of neonatal normal human foreskin-derived fibroblasts after irradiation with UVC and UVB light. It was found that the yield of dimerization and the ratio of T-T/C-T decreased from the UVC to the UVB region. Time-course studies of ODC-induction in the same cells indicated that the maximal activity after UVB irradiation was retarded compared to UVC exposure. For the UV-induced ODC-levels, however, no significant difference in maximal induction could be measured after UVC and UVB irradiation at fluences where comparable yields of thymine dimerization are produced. Similar ODC-maxima were obtained with strains from children, while cells from adults showed significantly less pronounced ODC induction, indicating that ODC-response decreases with age and may therefore be used as a marker of aging

  19. Electronic absorption study on acid-base equilibria for some pyrimidine derivatives containing semi- and thiosemicarbazone moiety

    Kılıç, H.

    2010-02-01

    The UV-vis spectra of recently synthesized 5-benzoyl-1-(methylphenylmethyleneamino)-4-phenyl-1H-pyrimidine-2-one, ( I), and 5-benzoyl-1-(methylphenylmethyleneamino)-4-phenyl-1H-pyrimidine-2-thione, ( II) were studied in aqueous methanol (5%, v/v methanol). The nature of the electronic transitions and the roles of carbonyl oxygen of I and thiocarbonyl sulfur of II on the behavior of UV-vis spectra were discussed. Acid-base equilibria of the compounds against varying pH and p Ka values related equilibria were determined at an ionic strength of 0.10 M by using the Henderson-Haselbalch equation. The mean acidity constants for the protonated forms of the compounds were determined as p Ka1 = 5.121, p Ka2 = 7.929 and p Ka3 = 11.130 for I and p Ka1 = 4.684, p Ka2 = 7.245 and p Ka3 = 10.630 for II. The preferred dissociation mechanisms were discussed based on UV-vis data and a mechanism was proposed for each compound.

  20. Three new double-headed nucleotides with additional nucleobases connected to C-5 of pyrimidines; synthesis, duplex and triplex studies.

    Kumar, Pawan; Sharma, Pawan K; Hansen, Jonas; Jedinak, Lukas; Reslow-Jacobsen, Charlotte; Hornum, Mick; Nielsen, Poul

    2016-02-15

    In the search for double-coding DNA-systems, three new pyrimidine nucleosides, each coded with an additional nucleobase anchored to the major groove face, are synthesized. Two of these building blocks carry a thymine at the 5-position of 2'-deoxyuridine through a methylene linker and a triazolomethylene linker, respectively. The third building block carries an adenine at the 6-position of pyrrolo-2'-deoxycytidine through a methylene linker. These double-headed nucleosides are introduced into oligonucleotides and their effects on the thermal stabilities of duplexes are studied. All studied double-headed nucleotide monomers reduce the thermal stability of the modified duplexes, which is partially compensated by using consecutive incorporations of the modified monomers or by flanking the new double-headed analogs with members of our former series containing propyne linkers. Also their potential in triplex-forming oligonucleotides is studied for two of the new double-headed nucleotides as well as the series of analogs with propyne linkers. The most stable triplexes are obtained with single incorporations of additional pyrimidine nucleobases connected via the propyne linker. PMID:26778611

  1. Stepwise charge transfer complexation of some pyrimidines with σ-acceptor iodine involving a new unconventional acceptor

    Rabie, Usama. M.; Mohamed, Ramadan. A.; Abou-El-Wafa, Moustafa. H.

    2007-11-01

    Interactions of some pyrimidine derivatives, 4-amino-2,6-dimethylpyrimidine, kyanmethin, (4AP), 2-amino-4,6-dimethylpyrimidine (2AP), 2-aminopyrimidine (AP), 2-amino-4-methylpyrimidine (AMP), 2-amino-4-methoxy-6-methylpyrimidine (AMMP), and 4-amino-5-chloro-2,6-dimethylpyrimidine (ACDP) as electron donors, with iodine (I 2), as a typical σ-electron acceptor, have been studied. Electronic absorption spectra of these interactions in several organic solvents of different polarities have performed instant appearance of clear charge transfer (CT) bands. Formation constants ( KCT), molar absorption coefficients ( ɛCT) and thermodynamic properties, Δ H, Δ S, and Δ G, of these interactions have been determined and discussed. Electronic absorption spectra of the solutions of the synthesized pyrimidines-iodine, P-I 2, CT complexes have shown the characteristic bands of the triiodide ion, I 3-. UV/vis spectral tracking of these interactions have shown that by lapse of time the first formed CT complex, P-I 2, is transformed to the corresponding triiodide complex, P +I.I 3-, then, the later interacts as a new unconventional acceptor and it forms a CT complex of the form (P).(P +I.I 3-). Elemental analyses of these solid complexes have indicated the stoichiometric ratio 2:2, or formally 1:1, P:I 2.

  2. Stepwise charge transfer complexation of some pyrimidines with sigma-acceptor iodine involving a new unconventional acceptor.

    Rabie, Usama M; Mohamed, Ramadan A; Abou-El-Wafa, Moustafa H

    2007-11-01

    Interactions of some pyrimidine derivatives, 4-amino-2,6-dimethylpyrimidine, kyanmethin, (4AP), 2-amino-4,6-dimethylpyrimidine (2AP), 2-aminopyrimidine (AP), 2-amino-4-methylpyrimidine (AMP), 2-amino-4-methoxy-6-methylpyrimidine (AMMP), and 4-amino-5-chloro-2,6-dimethylpyrimidine (ACDP) as electron donors, with iodine (I(2)), as a typical sigma-electron acceptor, have been studied. Electronic absorption spectra of these interactions in several organic solvents of different polarities have performed instant appearance of clear charge transfer (CT) bands. Formation constants (KCT), molar absorption coefficients (epsilonCT) and thermodynamic properties, DeltaH, DeltaS, and DeltaG, of these interactions have been determined and discussed. Electronic absorption spectra of the solutions of the synthesized pyrimidines-iodine, P-I2, CT complexes have shown the characteristic bands of the triiodide ion, I3*. UV/vis spectral tracking of these interactions have shown that by lapse of time the first formed CT complex, P-I2, is transformed to the corresponding triiodide complex, P(+)I.I3*, then, the later interacts as a new unconventional acceptor and it forms a CT complex of the form (P).(P+I.I3*). Elemental analyses of these solid complexes have indicated the stoichiometric ratio 2:2, or formally 1:1, P:I2. PMID:17317281

  3. Synthesis, characterization and spectrochemical studies on a few binuclear -oxo molybdenum(V) complexes of pyrimidine derived Schiff base ligands

    Samik Gupta; Somnath Roy; Tarak Nath Mandal; Kinsuk Das; Sangita Ray; Ray J Butcher; Susanta Kumar Kar

    2010-03-01

    Ten new binuclear singly oxo-bridged molybdenum complexes (complexes 1-10) were prepared using five pyrimidine derived Schiff base ligands and two Mo(V) precursors (NH4)2MoOCl5 and (NH4)2MoOBr5. The ligands are prepared by the condensation of 4,6-dimethyl 2-hydrazino pyrimidine with salicylaldehyde (for HL1), -hydroxy acetophenone (for HL2) and substituted salicylaldehydes (for HL3, HL4 and HL5) respectively. These ligands are already reported as good donors for Mo(VI) state. The -oxo Mo(V) complexes reported here bears a distorted octahedral geometry around each Mo atom with either N2O2Cl or N2O2Br chromophores. Fine variations in the spectroscopic behaviour of the complexes are observed in accordance with the varying electron donating properties of the ligands. All the complexes are unstable in solution and X-ray quality crystal of complex 1 could be isolated. All the complexes are characterized by IR and UV-Vis spectra.

  4. A Better Carbon Footprint Label

    Thøgersen, John; Nielsen, Kristian S.

    2016-01-01

    expected, price and carbon footprint were negatively related to choice. Further, participants preferred organic to non-organic coffee and certification by a public authority. The effect of the carbon label is significantly stronger the more environmentally concerned the consumer is. Using colors to...... indicate relative carbon footprint significantly increases carbon label effectiveness. Hence, a carbon footprint label is more effective if it uses traffic light colors to communicate the product's relative performance.......Based on insights from behavioral economics, it is suggested to extend carbon footprint labeling with information about relative performance, using the well-known “traffic light” color scheme to communicate relative performance. To test this proposition, the impact of a carbon footprint label on...

  5. Sublinear distance labeling for sparse graphs

    Alstrup, Stephen; Dahlgaard, Søren; Knudsen, Mathias Bæk Tejs; Porat, Ely

    A distance labeling scheme labels the $n$ nodes of a graph with binary strings such that, given the labels of any two nodes, one can determine the distance in the graph between the two nodes by looking only at the labels. A $D$-preserving distance labeling scheme only returns precise distances be...

  6. 21 CFR 201.71 - Magnesium labeling.

    2010-04-01

    ... 21 Food and Drugs 4 2010-04-01 2010-04-01 false Magnesium labeling. 201.71 Section 201.71 Food and... LABELING Labeling Requirements for Over-the-Counter Drugs § 201.71 Magnesium labeling. (a) The labeling of over-the-counter (OTC) drug products intended for oral ingestion shall contain the magnesium...

  7. Interstrand cross-link formation in duplex and triplex DNA by modified pyrimidines.

    Peng, Xiaohua; Hong, In Seok; Li, Hong; Seidman, Michael M; Greenberg, Marc M

    2008-08-01

    DNA interstrand cross-links have important biological consequences and are useful biotechnology tools. Phenylselenyl substituted derivatives of thymidine (1) and 5-methyl-2'-deoxycytidine (5) produce interstrand cross-links in duplex DNA when oxidized by NaIO4. The mechanism involves a [2,3]-sigmatropic rearrangement of the respective selenoxides to the corresponding methide type intermediates, which ultimately produce the interstrand cross-links. Determination of the rate constants for the selenoxide rearrangements indicates that the rate-determining step for cross-linking is after methide formation. Cross-linking by the thymidine derivative in duplex DNA shows a modest kinetic preference when flanked by pyrimidines as opposed to purines. In contrast, the rate constant for cross-link formation from 5 opposite dG in duplex DNA is strongly dependent upon the flanking sequence and, in general, is at least an order of magnitude slower than that for 1 in an otherwise identical sequence. Introduction of mispairs at the base pairs flanking 5 or substitution of the opposing dG by dI significantly increases the rate constant and yield for cross-linking, indicating that stronger hydrogen bonding between the methide derived from it and dG compared to dA and the respective electrophile derived from 1 limits reaction by increasing the barrier to rotation into the required syn-conformation. Incorporation of 1 or 5 in triplex forming oligonucleotides (TFOs) that utilize Hoogsteen base pairing also yields interstrand cross-links. The dC derivative produces ICLs approximately 10x faster than the thymidine derivative when incorporated at the 5'-termini of the TFOs and higher yields when incorporated at internal sites. The slower, less efficient ICL formation emanating from 1 is attributed to reaction at N1-dA, which requires local melting of the duplex. In contrast, 5 produces cross-links by reacting with N7-dG. The cross-linking reactions of 1 and 5 illustrate the versatility and

  8. How to Read a Nutrition Facts Label

    Full Text Available ... Under Control Figuring Out Food Labels Healthy Food Shopping If My Child Has Food Allergies, What Should ... for Parents Figuring Out Food Labels Smart Supermarket Shopping Figuring Out Fat and Calories Food Labels Contact ...

  9. Synthesis and biological screening of 5-{[(4,6-disubstituted pyrimidine-2-ylthio]methyl}-N-phenyl-1,3,4-thiadiazol-2-amines

    Azam M

    2008-01-01

    Full Text Available A number of substituted-a,β -unsaturated carbonyl compounds (1a-i were prepared by Claisen-Schmidt condensation of substituted acetophenone with selected araldehydes, which on cycloaddition with thiourea furnished 4,6-disubstituted pyrimidine-2-thiols (2a-i. Reaction of (2a-i with ethyl chloroacetate followed by condensation with hydrazine hydrate yielded 2-[(4,6-disubstituted pyrimidine-2-yl thio] acetohydrazides (4a-c. Condensation of compounds (4a-c with phenyl isothiocyanate gave 2-{[(4,6-disubstituted pyrimidine-2-yl thio] acetyl}-N-phenylhydrazinecarbothioamides (5a-c which on treatment with concentrated sulphuric acid afforded titled compounds 5-{(4,6-disubstituted pyrimidine-2-yl thio] methyl}-N-phenyl-1,3,4-thiadiazole-2-amines (6a-c. These compounds have been characterized on the basis of elemental analysis, IR, 1 H NMR and MS. Compounds have been evaluated for their anticancer and antioxidant activities. Compounds 2b, 2c and 6b exhibited significant antitumor activity against human breast cancer MCF 7 cell line. However, moderate antioxidant activity was observed with compounds 2c, 2d, 2g and 6b.

  10. A Novel and Efficient Five-Component Synthesis of Pyrazole Based Pyrido[2,3-d]pyrimidine-diones in Water: A Triply Green Synthesis

    Majid M. Heravi

    2016-04-01

    Full Text Available A novel one pot synthesis of pyrazolo[4′,3′:5,6]pyrido[2,3-d]pyrimidine-diones, via a five-component reaction, involving, hydrazine hydrate, ethyl acetoacetate, and 1,3-dimethyl barbituric acid, an appropriate aryl aldehydes and ammonium acetate catalyzed via both of heterogeneous and homogeneous catalysis in water, is reported.

  11. Stereoselective synthesis of 2'-purine and pyrimidine derivatives of 1',4'-anhydro-2'-deoxy D-arabitol and D-altritol

    YANG, Bing-Hui; WU, Xue-Jun

    2000-01-01

    A series of 2'-purine and pyrimidine derivatives of 1',4'-anhydro-2'-deoxy-D-arabitol (1) and 1', 4'-anhydro-2'-deoxy-Daltritoi (2) were synthesized regio- and stereo-selectively from D-sorbitol through some conversion in high yields.

  12. Mechanism for the abiotic synthesis of uracil via UV-induced oxidation of pyrimidine in pure H2O ices under astrophysical conditions

    The UV photoirradiation of pyrimidine in pure H2O ices has been explored using second-order Moeller-Plesset perturbation theory and density functional theory methods, and compared with experimental results. Mechanisms studied include those starting with neutral pyrimidine or cationic pyrimidine radicals, and reacting with OH radical. The ab initio calculations reveal that the formation of some key species, including the nucleobase uracil, is energetically favored over others. The presence of one or several water molecules is necessary in order to abstract a proton which leads to the final products. Formation of many of the photoproducts in UV-irradiated H2O:pyrimidine=20:1 ice mixtures was established in a previous experimental study. Among all the products, uracil is predicted by quantum chemical calculations to be the most favored, and has been identified in experimental samples by two independent chromatography techniques. The results of the present study strongly support the scenario in which prebiotic molecules, such as the nucleobase uracil, can be formed under abiotic processes in astrophysically relevant environments, namely in condensed phase on the surface of icy, cold grains before being delivered to the telluric planets, like Earth.

  13. Efficient Synthesis of 3,5,6,7-Tetrahydro-4H-cyclopenta[4,5] thieno[2,3-d]Pyrimidin-4-ones

    LIU Ming-guo; ZHONG Ying; DING Ming-wu

    2008-01-01

    The title compounds 3,5,6,7-tetrahydro-4H-cyclopenta[4,5]thieno[2,3-d]pyrimidin-4-ones(6) were synthesized by base catalytic reactions of secondary amines with carbodiimides 4,which were obtained from the aza-Wittig reaction of iminophosphoranes(3) with aromatic isoeyanates.

  14. Insight into the binding mode and the structural features of the pyrimidine derivatives as human A2A adenosine receptor antagonists.

    Zhang, Lihui; Liu, Tianjun; Wang, Xia; Wang, Jinan; Li, Guohui; Li, Yan; Yang, Ling; Wang, Yonghua

    2014-01-01

    The interaction of 278 monocyclic and bicyclic pyrimidine derivatives with human A2A adenosine receptor (AR) was investigated by employing molecular dynamics, thermodynamic analysis and three-dimensional quantitative structure-activity relationship (3D-QSAR) approaches. The binding analysis reveals that the pyrimidine derivatives are anchored in TM2, 3, 5, 6 and 7 of A2A AR by the aromatic stacking and hydrogen bonding interactions. The key residues involving Phe168, Glu169, and Asn253 stabilize the monocyclic and bicyclic cores of inhibitors. The thermodynamic analysis by molecular mechanics/Poisson Boltzmann surface area (MM-PBSA) approach also confirms the reasonableness of the binding modes. In addition, the ligand-/receptor-based comparative molecular similarity indices analysis (CoMSIA) models of high statistical significance were generated and the resulting contour maps correlate well with the structural features of the antagonists essential for high A2A AR affinity. A minor/bulky group with negative charge at C2/C6 of pyrimidine ring respectively enhances the activity for all these pyrimidine derivatives. Particularly, the higher electron density of the ring in the bicyclic derivatives, the more potent the antagonists. The obatined results might be helpful in rational design of novel candidate of A2A adenosine receptor antagonist for treatment of Parkinson's disease. PMID:23665268

  15. A Novel and Efficient Five-Component Synthesis of Pyrazole Based Pyrido[2,3-d]pyrimidine-diones in Water: A Triply Green Synthesis.

    Heravi, Majid M; Daraie, Mansoureh

    2016-01-01

    A novel one pot synthesis of pyrazolo[4',3':5,6]pyrido[2,3-d]pyrimidine-diones, via a five-component reaction, involving, hydrazine hydrate, ethyl acetoacetate, and 1,3-dimethyl barbituric acid, an appropriate aryl aldehydes and ammonium acetate catalyzed via both of heterogeneous and homogeneous catalysis in water, is reported. PMID:27043522

  16. One-pot synthesis and antibacterial activities of pyrazolo[4',3':5,6]pyrido[2,3-d]pyrimidine-dione derivatives.

    Bazgir, Ayoob; Khanaposhtani, Maryam Mohammadi; Soorki, Ali Abolhasani

    2008-11-01

    A one-pot and efficient method for the synthesis of pyrazolo[4',3':5,6]pyrido[2,3-d]pyrimidine-dione derivatives by condensation reaction of barbituric acids, 1H-pyrazol-5-amines and aldehydes under solvent-free conditions is reported. These products were evaluated in vitro for their antibacterial activities. PMID:18842404

  17. Novel one-pot, three-component synthesis of spiro[indoline-pyrazolo[4',3':5,6]pyrido[2,3-d]pyrimidine]trione library.

    Ghahremanzadeh, Ramin; Sayyafi, Maryam; Ahadi, Somayeh; Bazgir, Ayoob

    2009-01-01

    A one-pot method for the efficient and simple synthesis of the novel spiro[indoline-pyrazolo[4',3':5,6]pyrido[2,3-d]pyrimidine]trione derivatives by a three-component condensation reaction of barbituric acids, 1H-pyrazol-5-amines and isatins in aqueous media is reported. PMID:19425616

  18. Thioxopyrimidine in Heterocyclic Synthesis III: Synthesis and Properties of Some Novel Heterocyclic Chalcone Derivatives Containing a Thieno[2,3-d]pyrimidine-Based Chromophore

    Yuh Wen Ho

    2013-01-01

    Full Text Available Cyclization of 4-methyl-2-phenyl-6-thioxo-1,6-dihydropyrimidine-5-carbonitrile 1 with chloroacetone in DMF in the presence of excess potassium carbonate anhydrous gave the 1-(5-amino-4-methyl-2-phenylthieno[2,3-d]pyrimidin-6-ylethanone 3, which can react with 2,5-dimethoxytetrahydrofuran in glacial acetic acid producing the 1-[4-methyl-2-phenyl-5-(1H-pyrrol-1-ylthieno[2,3-d]pyrimidin-6-yl]ethanone 4. On the other hand, a series of novel 3-aryl-1-[4-methyl-2-phenyl-5-(1H-pyrrol-1-yl-thieno[2,3-d]pyrimidin-6-yl]prop-2-en-1-one chalcone dyes 6a—n were obtained by the condensation reaction of 1-[4-methyl-2-phenyl-5(1H-pyrrol-1-ylthieno[2,3-d]-pyrimidin-6-yl]ethanone 4 with appropriate aldehydes. The structures of chalcone dyes were characterized by IR, 1H NMR, mass, elemental analysis, and UV-Vis spectroscopy. The dyes were applied to polyester fibers for creating hues ranging from greenish-yellow to orange; their spectral characteristics, substituent effect in DMF solution, fastness properties, and colorimetric assessment are also discussed.

  19. MULTICOMPONENT AND REGIOSELECTIVE SYNTHESIS OF DIHYDROPYRAZOLO[1,5-a]PYRIMIDINES FROM AROMATIC ALDEHYDES, MELDRUM'S ACID AND AMINOPYRAZOLE CAN508

    Jedinák, L.; Kryštof, Vladimír; Trávníček, Z.; Cankař, P.

    2014-01-01

    Roč. 89, č. 8 (2014), s. 1892-1904. ISSN 0385-5414 R&D Projects: GA MŠk(CZ) LO1204 Institutional support: RVO:61389030 Keywords : Pyrazolo[1,5-a]pyrimidine * Cyclization * Multicomponent Reaction Subject RIV: CC - Organic Chemistry Impact factor: 1.079, year: 2014

  20. Nucleobases and Prebiotic Molecules in Organic Residues Produced from the Ultraviolet Photo-Irradiation of Pyrimidine in NH3 and H2O+NH3 Ices

    Nuevo, Michel; Milam, Stefanie N.; Sandford, Scott

    2012-01-01

    Although not yet identified in the interstellar medium (ISM), N-heterocycles including nucleobases the information subunits of DNA and RNA are present in carbonaceous chondrites, which indicates that molecules of biological interest can be formed in non-terrestrial environments via abiotic pathways. Recent laboratory experiments and ab-initio calculations have already shown that the irradiation of pyrimidine in pure H2O ices leads to the formation of a suite of oxidized pyrimidine derivatives, including the nucleobase uracil. In the present work, NH3:pyrimidine and H2O:NH3:pyrimidine ice mixtures with different relative proportions were irradiated with UV photons under astrophysically relevant conditions. Liquid- and gas-chromatography analysis of the resulting organic residues has led to the detection of the nucleobases uracil and cytosine, as well as other species of prebiotic interest such as urea and small amino acids. The presence of these molecules in organic residues formed under abiotic conditions supports scenarios in which extraterrestrial organics that formed in space and were subsequently delivered to telluric planets via comets and meteorites could have contributed to the inventory of molecules that triggered the first biological reactions on their surfaces.

  1. Mitochondrial-encoded membrane protein transcripts are pyrimidine-rich while soluble protein transcripts and ribosomal RNA are purine-rich

    Samuels David C

    2005-09-01

    Full Text Available Abstract Background Eukaryotic organisms contain mitochondria, organelles capable of producing large amounts of ATP by oxidative phosphorylation. Each cell contains many mitochondria with many copies of mitochondrial DNA in each organelle. The mitochondrial DNA encodes a small but functionally critical portion of the oxidative phosphorylation machinery, a few other species-specific proteins, and the rRNA and tRNA used for the translation of these transcripts. Because the microenvironment of the mitochondrion is unique, mitochondrial genes may be subject to different selectional pressures than those affecting nuclear genes. Results From an analysis of the mitochondrial genomes of a wide range of eukaryotic species we show that there are three simple rules for the pyrimidine and purine abundances in mitochondrial DNA transcripts. Mitochondrial membrane protein transcripts are pyrimidine rich, rRNA transcripts are purine-rich and the soluble protein transcripts are purine-rich. The transitions between pyrimidine and purine-rich regions of the genomes are rapid and are easily visible on a pyrimidine-purine walk graph. These rules are followed, with few exceptions, independent of which strand encodes the gene. Despite the robustness of these rules across a diverse set of species, the magnitude of the differences between the pyrimidine and purine content is fairly small. Typically, the mitochondrial membrane protein transcripts have a pyrimidine richness of 56%, the rRNA transcripts are 55% purine, and the soluble protein transcripts are only 53% purine. Conclusion The pyrimidine richness of mitochondrial-encoded membrane protein transcripts is partly driven by U nucleotides in the second codon position in all species, which yields hydrophobic amino acids. The purine-richness of soluble protein transcripts is mainly driven by A nucleotides in the first codon position. The purine-richness of rRNA is also due to an abundance of A nucleotides. Possible

  2. Labelling GM-free Products

    Punt, Maarten; Venus, Thomas; Wesseler, Justus

    2016-01-01

    Food suppliers in the EU must comply with labelling regulations for genetically modified organisms (GMOs). However, excluded from mandatory labelling are food products derived from animals fed with GM feed (mainly GM soybean in the EU). Because of this labelling exemption, consumers are unable to...... limited. The results indicate that for switching to ‘GM-free’ production, long-term effects such as the creation of a positive image or differentiation from competitors are more important for dairy companies than short-term effects such as higher sales or profit....

  3. Sustainability labels on food products

    Grunert, Klaus G; Hieke, Sophie; Wills, Josephine

    2014-01-01

    This study investigates the relationship between consumer motivation, understanding and use of sustainability labels on food products (both environmental and ethical labels), which are increasingly appearing on food products. Data was collected by means of an online survey implemented in the UK...... types of information available on food labels or as use inferred from the results of a choice-based conjoint analysis. Hierarchical regression indicated that use is related to both motivation and understanding, and that both motivation, understanding and use are affected by demographic characteristics...

  4. New labels for radiation therapy

    Kubota, Susumu; Mukai, Minoru; Kato, Hirotoshi (National Inst. of Radiological Sciences, Chiba (Japan))

    1992-12-01

    In simulating radiotherapy, the bone and trachea identified by plain X-P and the other organs, such as the esophagus and bladder, outlined by contrast medium have so far been used as labels. However, irradiation with a high therapeutic ratio is required for an intracorporeal insertion of artificial labels that are identified by X-ray fluoroscopy. For this purpose, metal clips and seed dummies are available, although they cause artifacts in CT scans. Therefore, the authors are using an acupuncture needle and lipiodol for tracing as new artificial labels, since both are identified by X-ray fluoroscopy and CT scan and create few artifacts. (J.P.N.).

  5. New labels for radiation therapy

    In simulating radiotherapy, the bone and trachea identified by plain X-P and the other organs, such as the esophagus and bladder, outlined by contrast medium have so far been used as labels. However, irradiation with a high therapeutic ratio is required for an intracorporeal insertion of artificial labels that are identified by X-ray fluoroscopy. For this purpose, metal clips and seed dummies are available, although they cause artifacts in CT scans. Therefore, the authors are using an acupuncture needle and lipiodol for tracing as new artificial labels, since both are identified by X-ray fluoroscopy and CT scan and create few artifacts. (J.P.N.)

  6. Crystal structure of ethyl 4-(2-meth­oxy­phen­yl)-6-methyl-2-sulfanyl­idene-1,2,3,4-tetra­hydro­pyrimidine-5-carboxyl­ate

    Shaaban K. Mohamed; Mague, Joel T.; Akkurt, Mehmet; Khodairy, Ahmed; Eman A. Ahmed

    2015-01-01

    In the title compound, C15H18N2O3S, the hydro­pyrimidine ring adopts a sofa conformation with the methine C atom as the flap. The benzene ring is almost perpendicular to the mean plane of the hydro­pyrimidine ring, making a dihedral angle of 85.51 (8)°, and the meth­oxy O atom lies over the centre of the pyrimidine ring. In the crystal, weak N—H⋯S inter­actions form a zigzag chain running along the b-axis direction.

  7. Design and synthesis of novel 5-substituted acyclic pyrimidine nucleosides as potent and selective inhibitors of hepatitis B virus.

    Kumar, Rakesh; Nath, Mahendra; Tyrrell, D Lorne J

    2002-05-01

    A novel class of 5-substituted acyclic pyrimidine nucleosides, 1-[(2-hydroxyethoxy)methyl]-5-(1-azidovinyl)uracil (9a), 1-[(2-hydroxy-1-(hydroxymethyl)ethoxy)methyl]-5-(1-azidovinyl)uracil (9b), and 1-[4-hydroxy-3-(hydroxymethyl)-1-butyl]-5-(1-azidovinyl)uracil (9c), were synthesized by regiospecific addition of bromine azide to the 5-vinyl substituent of the respective 5-vinyluracils (2a-c) followed by treatment of the obtained 5-(1-azido-2-bromoethyl) compounds (3a-c) with t-BuOK, to affect the base-catalyzed elimination of HBr. Thermal decomposition of 9b and 9c at 110 degrees C in dioxane yielded corresponding 5-[2-(1-azirinyl)]uracil analogues (10b,c). The 5-(1-azidovinyl)uracil derivatives 9a-c were found to exhibit potent and selective in vitro anti-HBV activity against duck hepatitis B virus (DHBV) infected primary duck hepatocytes at low concentrations (EC(50) = 0.01-0.1 microg/mL range). The most active anti-DHBV agent (9c), possessing a [4-hydroxy-3-(hydroxymethyl)-1-butyl] substituent at N-1, exhibited an activity (EC(50) of 0.01-0.05 microg/mL) comparable to that of reference compound (-)-beta-L-2',3'-dideoxy-3'-thiacytidine (3-TC) (EC(50) = 0.01-0.05 microg/mL). In contrast, related 5-[2-(1-azirinyl)]uracil analogues (10b,c) were devoid of anti-DHBV activity, indicating that an acyclic side chain at C-5 position of the pyrimidine ring is essential for anti-HBV activity. The pyrimidine nucleosides (9a-c, 10b,c) exhibited no cytotoxic activity against a panel of 60 human cancer cell lines. All of the compounds investigated did not show any detectable toxicity to several stationary and proliferating host cell lines or to mitogen stimulated proliferating human T lymphocytes, up to the highest concentration tested. PMID:11985471

  8. Quality control of labelled compounds

    Some advantages and disadvantages of methods used for quality control of organic labelled compounds (131I, 14C) are shortly discussed. The methods used are electrophoresis, ultraviolet and infrared spectrometry, radiogas and thin-layer chromatography. (author)

  9. Probing the metabolic network in bloodstream-form Trypanosoma brucei using untargeted metabolomics with stable isotope labelled glucose.

    Darren J Creek

    2015-03-01

    Full Text Available Metabolomics coupled with heavy-atom isotope-labelled glucose has been used to probe the metabolic pathways active in cultured bloodstream form trypomastigotes of Trypanosoma brucei, a parasite responsible for human African trypanosomiasis. Glucose enters many branches of metabolism beyond glycolysis, which has been widely held to be the sole route of glucose metabolism. Whilst pyruvate is the major end-product of glucose catabolism, its transamination product, alanine, is also produced in significant quantities. The oxidative branch of the pentose phosphate pathway is operative, although the non-oxidative branch is not. Ribose 5-phosphate generated through this pathway distributes widely into nucleotide synthesis and other branches of metabolism. Acetate, derived from glucose, is found associated with a range of acetylated amino acids and, to a lesser extent, fatty acids; while labelled glycerol is found in many glycerophospholipids. Glucose also enters inositol and several sugar nucleotides that serve as precursors to macromolecule biosynthesis. Although a Krebs cycle is not operative, malate, fumarate and succinate, primarily labelled in three carbons, were present, indicating an origin from phosphoenolpyruvate via oxaloacetate. Interestingly, the enzyme responsible for conversion of phosphoenolpyruvate to oxaloacetate, phosphoenolpyruvate carboxykinase, was shown to be essential to the bloodstream form trypanosomes, as demonstrated by the lethal phenotype induced by RNAi-mediated downregulation of its expression. In addition, glucose derivatives enter pyrimidine biosynthesis via oxaloacetate as a precursor to aspartate and orotate.

  10. LabeledIn: cataloging labeled indications for human drugs.

    Khare, Ritu; Li, Jiao; Lu, Zhiyong

    2014-12-01

    Drug-disease treatment relationships, i.e., which drug(s) are indicated to treat which disease(s), are among the most frequently sought information in PubMed®. Such information is useful for feeding the Google Knowledge Graph, designing computational methods to predict novel drug indications, and validating clinical information in EMRs. Given the importance and utility of this information, there have been several efforts to create repositories of drugs and their indications. However, existing resources are incomplete. Furthermore, they neither label indications in a structured way nor differentiate them by drug-specific properties such as dosage form, and thus do not support computer processing or semantic interoperability. More recently, several studies have proposed automatic methods to extract structured indications from drug descriptions; however, their performance is limited by natural language challenges in disease named entity recognition and indication selection. In response, we report LabeledIn: a human-reviewed, machine-readable and source-linked catalog of labeled indications for human drugs. More specifically, we describe our semi-automatic approach to derive LabeledIn from drug descriptions through human annotations with aids from automatic methods. As the data source, we use the drug labels (or package inserts) submitted to the FDA by drug manufacturers and made available in DailyMed. Our machine-assisted human annotation workflow comprises: (i) a grouping method to remove redundancy and identify representative drug labels to be used for human annotation, (ii) an automatic method to recognize and normalize mentions of diseases in drug labels as candidate indications, and (iii) a two-round annotation workflow for human experts to judge the pre-computed candidates and deliver the final gold standard. In this study, we focused on 250 highly accessed drugs in PubMed Health, a newly developed public web resource for consumers and clinicians on prevention

  11. Evidence for incorporation of intact dietary pyrimidine (but not purine) nucleosides into hepatic RNA.

    Berthold, H K; Crain, P F; Gouni, I; Reeds, P J; Klein, P D

    1995-01-01

    The absorption and metabolism of dietary nucleic acids have received less attention than those of other organic nutrients, largely because of methodological difficulties. We supplemented the rations of poultry and mice with the edible alga Spirulina platensis, which had been uniformly labeled with 13C by hydroponic culture in 13CO2. The rations were ingested by a hen for 4 wk and by four mice for 6 days; two mice were fed a normal diet and two were fed a nucleic acid-deficient diet. The anima...

  12. Stretches of alternating pyrimidine/purines and purines are respectively linked with pathogenicity and growth temperature in prokaryotes

    Ussery, David; Bohlin, J; Hardy, SP

    2009-01-01

    consequence of the chemical properties of purines and pyrimidines, a thorough statistical examination of the distributions of YR/RR stretches in sequenced prokaryotic chromosomes has to the best of our knowledge, not been undertaken. The aim of this study is to expand upon previous research by using...... regression analysis to investigate how AT content, habitat, growth temperature, pathogenicity, phyla, oxygen requirement and halotolerance correlated with the distribution of RR and YR stretches in prokaryotes. RESULTS: Our results indicate that RR and YR-stretches are differently distributed in prokaryotic...... associated with phylum, AT content, oxygen requirement, growth temperature and halotolerance. All associations described were statistically significant with p <0.001. CONCLUSION: Analysis of chromosomal distributions of RR/YR sequences in prokaryotes reveals a set of associations with environmental factors...

  13. Kinetics and mechanism of electron-induced splitting of a cyclobutane pyrimidine dimer with or without an electron acceptor

    YAN; Liqin(晏利琴); SONG; Qinhua(宋钦华); HEI; Xiaoming(黑晓明); WANG; Wenfeng(王文锋); GUO; Qingxiang(郭庆祥)

    2003-01-01

    Utilizing a pulse radiolysis equipment with time-resolved optical detector, kinetic processes of electron-induced splitting of cis-syn 1,3-dimethyluracil cyclobutane dimer (DMUD) in aqueous solution were investigated in the presence or absence of riboflavin (RF) or flavin adenine dinucleotide (FAD). It has been observed that the cyclobutane pyrimidine dimer reacting with hydrated electron splits spontaneously to give a monomer and a monomer radical anion, and the anion transfers one electron to RF or FAD. From the buildup kinetics of radical species, the rate constants of electron transfer from the monomer radical anion to RF and FAD have been determined. On the basis of comparison of the interactions between DMUD and hydrated electron in the presence and absence of RF or FAD, a chain reaction process in the absence of RF or FAD has been demonstrated.

  14. Crystal structure of 1-ethylpyrazolo[3,4-d]pyrimidine-4(5H-thione

    Mohammed El Fal

    2014-09-01

    Full Text Available In the title compound, C7H8N4S, the methyl C atom is displaced by 1.232 (7 Å from the mean plane of the pyrazolo[3,4-d]pyrimidine ring system (r.m.s. deviation = 0.007 Å. The N—N—C—Cm (m = methyl torsion angle is −60.3 (6°. In the crystal, molecules are linked by N—H...S hydrogen bonds, generating [010] chains, which are reinforced by C—H...N interactions. The chains are cross-linked by weak C—H...S hydrogen bonds, generating (001 sheets.

  15. Nuclear dynamics investigation of the initial electron transfer in the cyclobutane pyrimidine dimer lesion repair process by photolyases

    Joubert-Doriol, Loic; Olivucci, Massimo; Izmaylov, Artur F

    2016-01-01

    Photolyases are proteins capable of harvesting the sunlight to repair DNA damages caused by UV light. In this work we focus on the first step in the repair process of the cyclobutane pyrimidine dimer photoproduct (CPD) lesion, which is an electron transfer (ET) from a flavine cofactor to CPD, and study the role of various nuclear degrees of freedom (DOF) in this step. The ET step has been experimentally studied using transient spectroscopy and the corresponding data provide excellent basis for testing the quality of quantum dynamical models. Based on previous theoretical studies of electronic structure and conformations of the protein active site, we present a procedure to build a diabatic Hamiltonian for simulating the ET reaction in a molecular complex mimicking the enzyme's active site. We generate a reduced nuclear dimensional model that provides a first non-empirical quantum dynamical description of the structural features influencing the ET rate. By varying the nuclear DOF parametrization in the model t...

  16. Synthesis and Crystal Structure of 4-(4,6-dimethoxyl -pyrimidin-2-yl)-3-thiourea Carboxylic Acid Methyl Ester

    HUANG Jie; SONG Ji-Rong; REN Ying-Hui; XU Kang-Zhen; MA Hai-Xia

    2006-01-01

    The title compound 4-(4,6-dimethoxylpyrimidin-2-yl)-3-thiourea carboxylic acid methyl ester was synthesized by the reaction of 2-amino-4,6-dimethoxyl pyrimidine, potassium thiocyanate and methyl chloroformate in ethyl acetate. Single crystals suitable for X-ray measurement were obtained by recrystallization with the solvent of dimethyl formamide at the room temperature. The structure was characterized by elemental analysis and IR and determined by X-ray diffraction analysis. Crystallographic data: C9H12N4O4S, Mr = 272.29, monoclinic, space group C2/m with a = 1.6672(3), b = 0.66383(12), c = 1.1617(2) nm, β = 109.275(2)°, V = 1.2136(4) nm3, Dc = 1.490 g/cm3, μ = 0.281 mm-1, F(000) = 568, Z = 4, R1 = 0.0341and wR2 = 0.1042.

  17. Molecular interaction of the first 3 enzymes of the de novo pyrimidine biosynthetic pathway of Trypanosoma cruzi

    Highlights: ► An Escherichia coli strain co-expressing CPSII, ATC, and DHO of Trypanosoma cruzi was constructed. ► Molecular interactions between CPSII, ATC, and DHO of T. cruzi were demonstrated. ► CPSII bound with both ATC and DHO. ► ATC bound with both CPSII and DHO. ► A functional tri-enzyme complex might precede the establishment of the fused enzyme. -- Abstract: The first 3 reaction steps of the de novo pyrimidine biosynthetic pathway are catalyzed by carbamoyl-phosphate synthetase II (CPSII), aspartate transcarbamoylase (ATC), and dihydroorotase (DHO), respectively. In eukaryotes, these enzymes are structurally classified into 2 types: (1) a CPSII-DHO-ATC fusion enzyme (CAD) found in animals, fungi, and amoebozoa, and (2) stand-alone enzymes found in plants and the protist groups. In the present study, we demonstrate direct intermolecular interactions between CPSII, ATC, and DHO of the parasitic protist Trypanosoma cruzi, which is the causative agent of Chagas disease. The 3 enzymes were expressed in a bacterial expression system and their interactions were examined. Immunoprecipitation using an antibody specific for each enzyme coupled with Western blotting-based detection using antibodies for the counterpart enzymes showed co-precipitation of all 3 enzymes. From an evolutionary viewpoint, the formation of a functional tri-enzyme complex may have preceded—and led to—gene fusion to produce the CAD protein. This is the first report to demonstrate the structural basis of these 3 enzymes as a model of CAD. Moreover, in conjunction with the essentiality of de novo pyrimidine biosynthesis in the parasite, our findings provide a rationale for new strategies for developing drugs for Chagas disease, which target the intermolecular interactions of these 3 enzymes.

  18. T.C.G triplet in an antiparallel purine.purine.pyrimidine DNA triplex. Conformational studies by NMR.

    Dittrich, K; Gu, J; Tinder, R; Hogan, M; Gao, X

    1994-04-12

    The antiparallel purine.purine.pyrimidine DNA triplex, RRY6, which contains a T.C.G inverted triplet in the center of the sequence, was examined by proton and phosphorous two-dimensional NMR spectroscopy. The local conformation of the T.C.G triplet (T4.C11.G18) and the effect of this triplet on the global helical structure were analyzed in detail. The formation of the T.C.G triplet is confirmed by a set of cross-strand NOEs, including unusual cross-strand NOEs between the third strand and the pyrimidine strand as opposed to the purine strand of the duplex. NMR data suggest that the T.C.G triplet may be present in an equilibrium between a non-hydrogen-bonded form and a T(O4)-C(NH2) hydrogen-bonded form and that there is a distortion of the in-plane alignment of the three bases. The flanking G.G.C base triplets are well-defined on the 5'-side of T4, but somewhat interrupted on the 3'-side of T4. The effect of the third strand binding on the Watson-Crick duplex was probed by an NMR study of the free duplex RY6. NMR parameters are affected mostly around the T.C.G inversion site. The perturbations extend to at least two adjacent base triplets on either side. The binding of the third purine strand and the accommodation of a central T.C.G inversion in RRY6 does not require a readjustment in sugar pucker, which remains in the range of C2'-endo. 31P resonances of RRY6 distribute over a range of 2.2 ppm. The H-P coupling patterns of the third strand differ from those of the duplex. General spectral patterns defined by the marker protons of the RRY and YRY triplexes are compared. PMID:8155628

  19. Molecular interaction of the first 3 enzymes of the de novo pyrimidine biosynthetic pathway of Trypanosoma cruzi

    Nara, Takeshi, E-mail: tnara@juntendo.ac.jp [Department of Molecular and Cellular Parasitology, Juntendo University Graduate School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421 (Japan); Hashimoto, Muneaki; Hirawake, Hiroko [Department of Molecular and Cellular Parasitology, Juntendo University Graduate School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421 (Japan); Liao, Chien-Wei [Department of Molecular and Cellular Parasitology, Juntendo University Graduate School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421 (Japan); Department of Parasitology, Taipei Medical University, 250 Wu-Xing Street, Taipei 110, Taiwan, ROC (China); Fukai, Yoshihisa; Suzuki, Shigeo; Tsubouchi, Akiko; Morales, Jorge; Takamiya, Shinzaburo [Department of Molecular and Cellular Parasitology, Juntendo University Graduate School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421 (Japan); Fujimura, Tsutomu; Taka, Hikari; Mineki, Reiko [Division of Proteomics and Biomolecular Science, Biomedical Research Center, Juntendo University Graduate School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421 (Japan); Fan, Chia-Kwung [Department of Parasitology, Taipei Medical University, 250 Wu-Xing Street, Taipei 110, Taiwan, ROC (China); Inaoka, Daniel Ken [Department of Biomedical Chemistry, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033 (Japan); Inoue, Masayuki [Graduate School of Pharmaceutical Sciences, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033 (Japan); Tanaka, Akiko [Systems and Structural Biology Center, RIKEN, Tsurumi, Yokohama 230-0045 (Japan); Harada, Shigeharu [Department of Applied Biology, Graduate School of Science and Technology, Kyoto Institute of Technology, Sakyo-ku, Kyoto 606-8585 (Japan); Kita, Kiyoshi [Department of Biomedical Chemistry, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033 (Japan); and others

    2012-02-03

    Highlights: Black-Right-Pointing-Pointer An Escherichia coli strain co-expressing CPSII, ATC, and DHO of Trypanosoma cruzi was constructed. Black-Right-Pointing-Pointer Molecular interactions between CPSII, ATC, and DHO of T. cruzi were demonstrated. Black-Right-Pointing-Pointer CPSII bound with both ATC and DHO. Black-Right-Pointing-Pointer ATC bound with both CPSII and DHO. Black-Right-Pointing-Pointer A functional tri-enzyme complex might precede the establishment of the fused enzyme. -- Abstract: The first 3 reaction steps of the de novo pyrimidine biosynthetic pathway are catalyzed by carbamoyl-phosphate synthetase II (CPSII), aspartate transcarbamoylase (ATC), and dihydroorotase (DHO), respectively. In eukaryotes, these enzymes are structurally classified into 2 types: (1) a CPSII-DHO-ATC fusion enzyme (CAD) found in animals, fungi, and amoebozoa, and (2) stand-alone enzymes found in plants and the protist groups. In the present study, we demonstrate direct intermolecular interactions between CPSII, ATC, and DHO of the parasitic protist Trypanosoma cruzi, which is the causative agent of Chagas disease. The 3 enzymes were expressed in a bacterial expression system and their interactions were examined. Immunoprecipitation using an antibody specific for each enzyme coupled with Western blotting-based detection using antibodies for the counterpart enzymes showed co-precipitation of all 3 enzymes. From an evolutionary viewpoint, the formation of a functional tri-enzyme complex may have preceded-and led to-gene fusion to produce the CAD protein. This is the first report to demonstrate the structural basis of these 3 enzymes as a model of CAD. Moreover, in conjunction with the essentiality of de novo pyrimidine biosynthesis in the parasite, our findings provide a rationale for new strategies for developing drugs for Chagas disease, which target the intermolecular interactions of these 3 enzymes.

  20. Mindboggle: Automated brain labeling with multiple atlases

    To make inferences about brain structures or activity across multiple individuals, one first needs to determine the structural correspondences across their image data. We have recently developed Mindboggle as a fully automated, feature-matching approach to assign anatomical labels to cortical structures and activity in human brain MRI data. Label assignment is based on structural correspondences between labeled atlases and unlabeled image data, where an atlas consists of a set of labels manually assigned to a single brain image. In the present work, we study the influence of using variable numbers of individual atlases to nonlinearly label human brain image data. Each brain image voxel of each of 20 human subjects is assigned a label by each of the remaining 19 atlases using Mindboggle. The most common label is selected and is given a confidence rating based on the number of atlases that assigned that label. The automatically assigned labels for each subject brain are compared with the manual labels for that subject (its atlas). Unlike recent approaches that transform subject data to a labeled, probabilistic atlas space (constructed from a database of atlases), Mindboggle labels a subject by each atlas in a database independently. When Mindboggle labels a human subject's brain image with at least four atlases, the resulting label agreement with coregistered manual labels is significantly higher than when only a single atlas is used. Different numbers of atlases provide significantly higher label agreements for individual brain regions. Increasing the number of reference brains used to automatically label a human subject brain improves labeling accuracy with respect to manually assigned labels. Mindboggle software can provide confidence measures for labels based on probabilistic assignment of labels and could be applied to large databases of brain images

  1. 49 CFR 172.407 - Label specifications.

    2010-10-01

    ... line outer border to meet the requirements of § 172.406(d) of this subpart. (c) Size. (1) Each diamond..., numbers, and border must be shown in black on a label except that— (i) White may be used on a label with a... the CORROSIVE label. (iii) White may be used for the symbol for the ORGANIC PEROXIDE label. (3)...

  2. Radio labeling with pre-assigned frequencies

    Bodlaender, H.L.; Broersma, H.J.; Fomin, F.V.; Pyatkin, A.V.; Woeginer, G.J.

    2007-01-01

    A radio labeling of a graph G is an assignment of pairwise distinct, positive integer labels to the vertices of G such that labels of adjacent vertices differ by at least 2. The radio labeling problem (RL) consists in determining a radio labeling that minimizes the maximum label that is used (the so-called span of the labeling). RL is a well-studied problem, mainly motivated by frequency assignment problems in which transmitters are not allowed to operate on the same frequency channel. We con...

  3. Radio labeling with pre-assigned frequencies

    Bodlaender, H.L.; Broersma, H.J.; Fomin, F.V.; Pyatkin, A.V.; Woeginger, G.J.

    2002-01-01

    A radio labeling of a graph $G$ is an assignment of pairwise distinct, positive integer labels to the vertices of $G$ such that labels of adjacent vertices differ by at least $2$. The radio labeling problem (\\mbox{\\sc RL}) consists in determining a radio labeling that minimizes the maximum label that is used (the so-called span of the labeling). \\mbox{\\sc RL} is a well-studied problem, mainly motivated by frequency assignment problems in which transmitters are not allowed to operate on the sa...

  4. Photoaffinity Labeling of Plasma Proteins

    Masaki Otagiri

    2013-11-01

    Full Text Available Photoaffinity labeling is a powerful technique for identifying a target protein. A high degree of labeling specificity can be achieved with this method in comparison to chemical labeling. Human serum albumin (HSA and α1-acid glycoprotein (AGP are two plasma proteins that bind a variety of endogenous and exogenous substances. The ligand binding mechanism of these two proteins is complex. Fatty acids, which are known to be transported in plasma by HSA, cause conformational changes and participate in allosteric ligand binding to HSA. HSA undergoes an N-B transition, a conformational change at alkaline pH, that has been reported to result in increased ligand binding. Attempts have been made to investigate the impact of fatty acids and the N-B transition on ligand binding in HSA using ketoprofen and flunitrazepam as photolabeling agents. Meanwhile, plasma AGP is a mixture of genetic variants of the protein. The photolabeling of AGP with flunitrazepam has been utilized to shed light on the topology of the protein ligand binding site. Furthermore, a review of photoaffinity labeling performed on other major plasma proteins will also be discussed. Using a photoreactive natural ligand as a photolabeling agent to identify target protein in the plasma would reduce non-specific labeling.

  5. Radioisotope method for leucocyte labelling

    Whole blood leukocytes were labelled with 99mTc-sulphocolloid, which was selectively deposited in phagocytizing polymorphonuclear cells. To achieve optimal phagocytosis, the authors prepared 99mTc sulphocoloid from a Bulgarian kit. The required size of the colloid particles (1,2 μm) was achieved after 90-120 min storage at room temperature without rotation. Leucocytes were labelled by a proposed by the authors original method: to 10 ml heparinized blood 0,26-0,30 GB 99mTc sulphocolloid was added, incubated for 60 min; the free sulphocolloid was centrifuged in the syringe. The labelled cell sediment was suspended in physiological saline and re-injected. In a study of 16 patients on gamma camera, suspected of having inflammatory processes, the mean labelling effectiveness was 59%, similar to the one reported by other authors, who used similar technique and ready-made kits. Eight patients had positive finding, the inflammatory process in 7 being visualized as early as on hour 2 or 3 and in 1 on hour 24. The new method developed for specific leucocyte labelling with the use of Bulgarian kit may gain acceptance in the visualization of vague inflammatory processes. 3 figs., 4 refs

  6. 49 CFR 172.430 - POISON label.

    2010-10-01

    ... 49 Transportation 2 2010-10-01 2010-10-01 false POISON label. 172.430 Section 172.430... SECURITY PLANS Labeling § 172.430 POISON label. (a) Except for size and color, the POISON label must be as follows: EC02MR91.029 (b) In addition to complying with § 172.407, the background on the POISON label...

  7. Nutrition Labeling Using a Computer Program

    Metzger, Lloyd E.

    The 1990 Nutrition Labeling and Education Act mandated nutritional labeling of most foods. As a result, a large portion of food analysis is performed for nutritional labeling purposes. A food labeling guide and links to the complete nutritional labeling regulations are available online at http://vm.cfsan.fda.gov/˜dms/flg-toc.html. However, interpretation of these regulations and the appropriate usage of rounding rules, available nutrient content claims, reference amounts, and serving size can be difficult.

  8. EFSA Panel on Food Contact Materials, Enzymes, Flavourings and Processing Aids (CEF); Scientific Opinion on Flavouring Group Evaluation 301 (FGE.301): A sulphur substituted pyrimidin-derivative and its hydrochloride salt

    Larsen, John Christian; Nørby, Karin Kristiane; Beltoft, Vibe Meister;

    The Panel on Food Contact Materials, Enzymes, Flavourings and Processing Aids of the European Food Safety Authority was requested to evaluate two flavouring substances, 4-amino-5,6-dimethylthieno[2,3-d]pyrimidin-2(1H)-one [FL-no: 16.116] and 4-amino-5,6-dimethylthieno[2,3-d]pyrimidin-2(1H...

  9. Positron emitter labeled enzyme inhibitors

    This invention involves a new strategy for imagining and mapping enzyme activity in the living human and animal body using positron emitter-labeled suicide enzyme inactivators or inhibitors which become covalently bound to the enzyme as a result of enzymatic catalysis. Two such suicide inactivators for monoamine oxidase have been labeled with carbon-11 and used to map the enzyme subtypes in the living human and animal body using PET. By using positron emission tomography to image the distribution of radioactivity produced by the body penetrating radiation emitted by carbon-11, a map of functionally active monoamine oxidase activity is obtained. Clorgyline and L-deprenyl are suicide enzyme inhibitors and irreversibly inhibit monoamine oxidase. When these inhibitors are labeled with carbon-11 they provide selective probes for monoamine oxidase localization and reactivity in vivo using positron emission tomography

  10. Pyrimidine and nucleoside gamma-esters of L-Glu-Sar

    Eriksson, André H; Elm, Peter L; Begtrup, Mikael;

    2005-01-01

    permeable supports. Affinity was estimated in a competition assay, using [14C] labelled Gly-Sar (glycylsarcosine). Translocation was measured as pHi-changes induced by the substrates using the fluorescent probe BCECF and an epifluorescence microscope setup. All dipeptide derivatives released the model drugs...... compounds showed good affinity to hPEPT1, but the Compounds I and III showed not to be translocated by hPEPT1. The translocation of the l-Glu-Sar derivative of acyclovir, l-Glu(acyclovir)-Sar was also investigated and showed not to take place. Consequently, l-Glu-Sar seems to be a poor pro-moiety for hPEPT1...

  11. Configuration spaces with summable labels

    Salvatore, Paolo

    1999-01-01

    Let M be an n-manifold, and let A be a space with a partial sum behaving as an n-fold loop sum. We define the space C(M;A) of configurations in M with summable labels in A via operad theory. Some examples are symmetric products, labelled configuration spaces, and spaces of rational curves. We show that C(I^n,dI^n;A) is an n-fold delooping of C(I^n;A), and for n=1 it is the classifying space by Stasheff. If M is compact, parallelizable, and A is path connected, then C(M;A) is homotopic to the ...

  12. Denture labeling: A new approach

    Pardeep K Bansal

    2011-01-01

    Full Text Available The need for denture labeling is important for forensic and social reasons in case patients need to be identified individually. The importance of denture marking has long been acknowledged by the dental profession. Over the years, various denture marking systems have been reported in the literature, but none till date fulfills all the prescribed ADA specifications. A simple, easy, inexpensive procedure for marking accurate identification marks on dentures with a lead foil is described here. The label caring the patient information is incorporated in the acrylic resin during the denture processing.

  13. Connected Component Labeling Using Components Neighbors-Scan Labeling Approach

    Akmal Rakhmadi

    2010-01-01

    Full Text Available Problem statement: Many approaches have been proposed in previous such as the classic sequential connected components labeling algorithm which is relies on two subsequent raster-scans of a binary image. This method produced good performance in terms of accuracy, but because of the implementation of the image processing systems now requires faster process of the computer, the speed of this technique’s process has become an important issue. Approach: A computational approach, called components neighbors-scan labeling algorithm for connected component labeling was presented in this study. This algorithm required scanning through an image only once to label connected components. The algorithm started by scanning from the head of the component’s group, before tracing all the components neighbors by using the main component’s information. This algorithm had desirable characteristics, it is simple while promoted accuracy and low time consuming. By using a table of components, this approach also gave other advantages as the information for the next higher process. Results: The approach had been tested with a collection of binary images. In practically all cases, the technique had successfully given the desired result. Averagely, from the results the algorithm increased the speed around 67.4% from the two times scanning method. Conclusion: Conclusion from the comparison with the previous method, the approach of components neighbors-scan for connected component labeling promoted speed, accuracy and simplicity. The results showed that the approach has a good performance in terms of accuracy, the time consumed and the simplicity of the algorithm.

  14. Synthesis, Antibacterial and Antitubercular Activities of Some 5H-Thiazolo[3,2-a]pyrimidin-5-ones and Sulfonic Acid Derivatives

    Dong Cai

    2015-09-01

    Full Text Available A series of 5H-thiazolo[3,2-a]pyrimidin-5-ones were synthesized by the cyclization reactions of S-alkylated derivatives in concentrated H2SO4. Upon treatment of S-alkylated derivatives at different temperatures, intramolecular cyclization to 7-(substituted phenylamino-5H-thiazolo[3,2-a]pyrimidin-5-ones or sulfonation of cyclized products to sulfonic acid derivatives occurred. The structures of the target compounds were confirmed by IR, 1H-NMR, 13C-NMR and HRMS studies. The compounds were evaluated for their preliminary in vitro antibacterial activity against some Gram-positive and Gram-negative bacteria and screened for antitubercular activity against Mycobacterium tuberculosis by the broth dilution assay method. Some compounds showed good antibacterial and antitubercular activities.

  15. Synthesis, Antibacterial and Antitubercular Activities of Some 5H-Thiazolo[3,2-a]pyrimidin-5-ones and Sulfonic Acid Derivatives.

    Cai, Dong; Zhang, Zhi-Hua; Chen, Yu; Yan, Xin-Jia; Zou, Liang-Jing; Wang, Ya-Xin; Liu, Xue-Qi

    2015-01-01

    A series of 5H-thiazolo[3,2-a]pyrimidin-5-ones were synthesized by the cyclization reactions of S-alkylated derivatives in concentrated H₂SO₄. Upon treatment of S-alkylated derivatives at different temperatures, intramolecular cyclization to 7-(substituted phenylamino)-5H-thiazolo[3,2-a]pyrimidin-5-ones or sulfonation of cyclized products to sulfonic acid derivatives occurred. The structures of the target compounds were confirmed by IR, ¹H-NMR, (13)C-NMR and HRMS studies. The compounds were evaluated for their preliminary in vitro antibacterial activity against some Gram-positive and Gram-negative bacteria and screened for antitubercular activity against Mycobacterium tuberculosis by the broth dilution assay method. Some compounds showed good antibacterial and antitubercular activities. PMID:26378507

  16. Syntheses and properties of new herbicidal 2-arylthio-1,2,4-tria-zolo[ 1,5-a ] pyrimidine derivatives

    YANG, Guang-Fu(杨光富); LU, Rong-Jian(陆荣键); FEI, Xue-Ning(费学宁); YANG, Hua-Zheng(杨华铮)

    2000-01-01

    In search of novel herbicides with high activity, a series of 2-arylthio-1,2,4-triazolo[1,5-a]pyrimidines (3) were synthe-sized by cyclization of 5-amino-3-arylthio-1,2,4-triazoles with 1,3-diketones or by the nucleophilic substitution of substituted thiophenols with 2-methylsulfonyl-1, 2, 4-triazolo [1, 5-a ]-pyrimidine. The structures of all compounds prepared were confirmed by 1H NMR and MS spectroscopy along with elemental analyses. Preliminary bioassays indicated that some of the compounds 3 had good herbicidal activity against rape. In addition, the regioselectivity in the reaction of 5-amino-3-sub-stituted aryithio-1,2,4-triazoles with benzoylacetone was studied.

  17. Crystal structure of methyl 4-(2-fluoro-phenyl)-6-methyl-2-sulfanylidene-1,2,3,4-tetra-hydro-pyrimidine-5-carb-oxy-late.

    Krishnamurthy, M S; Begum, Noor Shahina

    2015-11-01

    In the title compound, C13H13FN2O2S, the pyrimidine ring adopts a twist-boat conformation with the MeCN and methine-C atoms displaced by 0.0938 (6) and 0.2739 (3) Å, respectively, from the mean plane through the other four atoms of the ring. The 2-fluoro-benzene ring is positioned axially and forms a dihedral angle of 89.13 (4)° with the mean plane through the pyrimidine ring. The crystal structure features N-H⋯O, N-H⋯S and C-H⋯O hydrogen bonds that link mol-ecules into supra-molecular chains along the b axis. These chains are linked into a layer parallel to (10-1) by C-H⋯π inter-actions; layers stack with no specific inter-actions between them. PMID:26594554

  18. Efficient synthesis of spiro[chromeno[2,3-d]pyrimidine-5,3'-indoline]-tetraones by a one-pot and three-component reaction.

    Jadidi, Khosrow; Ghahremanzadeh, Ramin; Bazgir, Ayoob

    2009-01-01

    An efficient one-pot synthesis of novel 8,9-dihydrospiro[chromeno[2,3-d]pyrimidine-5,3'-indoline]-2,2',4,6(1H,3H,7H)-tetraone derivatives by a three-component condensation reaction of barbituric acids, isatins and cyclohexane-1,3-diones in refluxing water in the presence of p-TSA for 10 h is reported. Two cyclohexane-1,3-diones, three barbituric acids, and eight substituted isatins were chosen for the library validation. Reaction of 5,5-dimethyl-cyclohexane-1,3-dione and acenaphthylene-1,2-dione with barbituric acids resulted in the formation of spiro[acenaphthylene-1,5'-chromeno[2,3-d]pyrimidine] derivatives. PMID:19239200

  19. Thioxopyrimidine in Heterocyclic Synthesis III: Synthesis and Properties of Some Novel Heterocyclic Chalcone Derivatives Containing a Thieno[2,3-d]pyrimidine-Based Chromophore

    Yuh Wen Ho; Wei Hua Yao

    2013-01-01

    Cyclization of 4-methyl-2-phenyl-6-thioxo-1,6-dihydropyrimidine-5-carbonitrile 1 with chloroacetone in DMF in the presence of excess potassium carbonate anhydrous gave the 1-(5-amino-4-methyl-2-phenylthieno[2,3-d]pyrimidin-6-yl)ethanone 3, which can react with 2,5-dimethoxytetrahydrofuran in glacial acetic acid producing the 1-[4-methyl-2-phenyl-5-(1H-pyrrol-1-yl)thieno[2,3-d]pyrimidin-6-yl]ethanone 4. On the other hand, a series of novel 3-aryl-1-[4-methyl-2-phenyl-5-(1H-pyrrol-1-yl)-thieno[...

  20. VUV photophysics and dissociative photoionization of pyrimidine, purine, imidazole and benzimidazole in the 7-18 eV photon energy range

    Schwell, Martin [Laboratoire Interuniversitaire des Systemes Atmospheriques (LISA), CNRS-UMR 7583, Universite Paris 7 and 12, 61 Avenue du General de Gaulle, 94010 Creteil (France)], E-mail: schwell@lisa.univ-paris12.fr; Jochims, Hans-Werner; Baumgaertel, Helmut [Institut fuer Physikalische und Theoretische Chemie der Freien Universitaet Berlin, Takustr. 3, Berlin 14195 (Germany); Leach, Sydney [Laboratoire d' Etude du Rayonnement et de la Matiere en Astrophysique (LERMA), CNRS-UMR 8112, Observatoire de Paris-Meudon, 5 Place Jules-Janssen, 92195 Meudon (France)], E-mail: Sydney.Leach@obspm.fr

    2008-11-03

    Photoionization mass spectrometry is used to study ionization processes and fragmentation pathways of four prebiotic species, pyrimidine, purine, imidazole and benzimidazole, in the 7-18 eV photon energy region, with synchrotron radiation as excitation source. These molecules are possible precursors of the nucleic acid bases that occur in DNA and RNA. Ionization energies and ion appearance energies are reported. They are compared with electron impact and other studies and are discussed in terms of the electronic and nuclear structures of these species and their cations. The ion appearance energies, in conjunction with thermochemical data, were used to propose dissociative photoionization pathways, principally involving loss of HCN molecules in each of the four species. Astrophysical implications of the results concern the prospects for observation and survival of these molecules in the interstellar medium, in comets and in meteorites. Suggestions are made concerning suitable sites for radioastronomical searches for these purines and pyrimidines.

  1. Synthesis of 4-aryl-4,5-dihydro-1-indeno[1,2-]pyrimidines by Biginelli condensation and their antibacterial activities

    Ramandeep Kaur; Monika Bansal; Balbir Kaur; Tulika Mishra; Aruna Bhatia

    2011-07-01

    A simple and efficient method has been developed for the synthesis of series of 4-aryl-1,3,4,5-tetrahydro-2-indeno[1,2-]pyrimidine-2-thiones through Biginelli’s one-pot multicomponent condensation reaction via microwave irradiations. Then, these thiones were converted to their S-alkylated/aralkylated derivatives. The prepared heterocyclic products were structurally confirmed by analytical and spectral data and evaluated for their antibacterial activities. The results showed that this skeletal framework exhibited marked potency as antibacterial agents. The compound 2-(Ethylthio)-4-(4-Hydroxy-3-methoxyphenyl)-4,5-dihydro-1-indeno[1,2-]pyrimidines 4b have shown antibacterial activity towards all the seven clinical isolates used.

  2. Synthesis and antiviral activity of 2,4-diamino-5-cyano-6-[2-(phosphonomethoxy)ethoxy]pyrimidine and related compounds

    Hocková, Dana; Holý, Antonín; Masojídková, Milena; Andrei, G.; Snoeck, R.; De Clercq, E.; Balzarini, J.

    2004-01-01

    Roč. 12, č. 12 (2004), s. 3197-3202. ISSN 0968-0896 R&D Projects: GA AV ČR IBS4055109 Grant ostatní: ISEP/FORTIS(US) GOA -00/12; European Commission(XE) HPAW-2002-90001 Institutional research plan: CEZ:AV0Z4055905 Keywords : nucleotide analogues * antiviral * pyrimidines Subject RIV: CC - Organic Chemistry Impact factor: 2.018, year: 2004

  3. Sonogashira cross-coupling in the synthesis of acyclic nucleoside phosphonates: preparation of 6-[(phosphonomethoxy)alkynyl]- and 6-[(phosphonomethoxy)alkyl]pyrimidines

    Hocková, Dana; Masojídková, Milena; Holý, Antonín

    2005-01-01

    Roč. 70, č. 2 (2005), 247-257. ISSN 0010-0765 R&D Projects: GA AV ČR(CZ) IBS4055109 Grant ostatní: René Descartes Prize 2001(XE) HPAW-2002-90001 Institutional research plan: CEZ:AV0Z40550506 Keywords : nucleotide analogues * acyclic nucleoside phosphonates * pyrimidines Subject RIV: CC - Organic Chemistry Impact factor: 0.949, year: 2005

  4. 3-Benzyl-6-benzyl­amino-1-methyl-5-nitro-1,2,3,4-tetra­hydro­pyrimidine

    Surya Prakash Rao, H.; Sathishkumar, R.; Sarathbabu, M.; Manivel, P.; Kannan, M; Krishna, R.

    2010-01-01

    In the title compound, C19H22N4O2, the tetra­hydro­pyrimidine ring adopts an envelope conformation (with the N atom connected to the benzyl group representing the flap). This benzyl group occupies a quasi-axial position. The two benzyl groups lie over the tetra­hydro­pyridimidine ring. The amino group is a hydrogen-bond donor to the nitro group.

  5. Triple helix formation: binding avidity of acridine-conjugated AG motif third strands containing natural, modified and surrogate bases opposed to pyrimidine interruptions in a polypurine target.

    Orson, F M; Klysik, J; Bergstrom, D E; Ward, B; Glass, G A; P. Hua; Kinsey, B M

    1999-01-01

    A critical issue for the general application of triple-helix-forming oligonucleotides (TFOs) as modulators of gene expression is the dramatically reduced binding of short TFOs to targets that contain one or two pyrimidines within an otherwise homopurine sequence. Such targets are often found in gene regulatory regions, which represent desirable sites for triple helix formation. Using intercalator-conjugated AG motif TFOs, we compared the efficacy and base selectivity of 13 different bases or ...

  6. Catalyst free synthesis of fused pyrido[2,3-d]pyrimidines and pyrazolo[3,4-b]pyridines in water

    Abbas Rahmati; Zahra Khalesi

    2012-01-01

    A one-pot,three-component condensation reaction of an aldehyde,benzoyl acetonitrile (3-oxo-3-phenylpropane nitrile) and 6-amino-1,3-dimethylpyrimidine-2,4(1H,3H)-dione or 3-methyl-1-phenyl-1H-pyrazol-5-amine in water to give fused pyrido[2,3-d]pyrimidines and pyrazolo[3,4-b]pyridines in high yields without any catalyst,is described.

  7. A copper-catalyzed one-pot, three-component tandem conjugative alkynylation/6-endo cyclization sequence: access to pyrano[2,3-d]-pyrimidines.

    Rajesh, Nimmakuri; Prajapati, Dipak

    2015-04-28

    A copper catalyzed one-pot, three component reaction between barbituric acid, aldehydes and terminal alkynes has been developed for the construction of pyrano[2,3-d]pyrimidines via a tandem conjugative alkynylation/6-endo cyclization pattern. Screening of barbituric acid derived organic acceptors in conjugative alkynylation reaction and the synthetic applicability of conjugative addition products under one-pot conditions were documented for the first time. PMID:25799181

  8. One-pot, three-component synthesis of a library of spirooxindole-pyrimidines catalyzed by magnetic nanoparticle supported dodecyl benzenesulfonic acid in aqueous media.

    Deng, Jia; Mo, Li-Ping; Zhao, Fei-Yang; Zhang, Zhan-Hui; Liu, Shou-Xin

    2012-05-14

    Dodecyl benzenesulfonic acid functionalized silica-coated magnetic nanoparticles (γ-Fe2O3@SiO2-DDBSA) were readily prepared and identified as an efficient catalyst for the synthesis of a library of spirooxindole-pyrimidine derivatives by three-component condensation reaction of barbituric acids, isatins and cyclohexane-1,3-diones. The aqueous reaction medium, easy recovery of the catalyst using an external magnet, and high yields make the protocol sustainable and economic. PMID:22533528

  9. 1-Benzyl-6-phenyl­imino-5-(pyrrol-2-yl­idene)hexa­hydro­pyrimidine-2,4-dione

    Tamazyan, Rafael; Ayvazyan, Armen; Martirosyan, Vahan; Avagyan, Kristine; Martirosyan, Ashot

    2008-01-01

    In the title compound, C21H20N4O2, a potential anti-human immunodeficiency virus type 1 (HIV-1) non-nucleoside reverse transcriptase inhibitor, the pyrrolidine ring adopts an envelope conformation, while the hydrogenated pyrimidine ring adopts a weakly expressed twist conformation. The mol­ecules are connected into infinite chains via N—H⋯O hydrogen bonds. PMID:21201507

  10. Synthesis, Dimeric Crystal Structure, and Biological Activities of N-(4-Methyl-6-oxo-1,6-dihydro-pyrimidin-2-yl)-N-(2-trifluoromethyl-phenyl)-guanidine

    2006-01-01

    The title compound, N-(4-methyl-6-oxo-1,6-dihydro-pyrimidin-2-yl)-N′-(2-trifluoromethyl-phenyl)-guanidine, was synthesized and its structure was confirmed by using IR, MS, 1H NMR, and elemental analysis. The single crystal structure of the title compound was determined by X-ray diffraction. The preliminary biological test showed that the synthesized compound has a weak herbicidal activity.

  11. Third party labeling and the consumer decision process: the case of the PGI European label

    Larceneux, Fabrice; Carpenter, Marie

    2008-01-01

    The objective of this research is to explore the decision-making process of consumers when faced with food products that have values-based labels. An experimental methodology was used to test the impact of a label of origin guaranteed by the European Union, the Protected Geographic Indications (PGI) label. Consumers' reactions to two different products were investigated with four different presentations: without a specific label, with a simple regional label, with both a regional label and th...

  12. Nutrition Marketing on Food Labels

    Nutrition marketing may influence purchasing behavior and thereby be a factor in the obesity epidemic. Very little peer-reviewed research has been published which investigates the relationship between nutrition marketing on food labels and consumer behavior. The purpose of this paper was to give an ...

  13. Improving the energy labelling scheme

    Gram-Hanssen, Kirsten; Christensen, Toke Haunstrup

    This report summarises the main results of an EU project on consumer response to energy labels in buildings. This report is mainly directed at Danish policy makers. The main focus is therefore on results that are relevant from a Danish point of view and on how they can be used to further strength...

  14. Identification of a large genomic region in UV-irradiated human cells which has fewer cyclobutane pyrimidine dimers than most genomic regions

    Size separation after UV-endonuclease digestion of DNA from UV-irradiated human cells using denaturing conditions fractionates the genome based on cyclobutane pyrimidine dimer content. We have examined the largest molecules available (50-80 kb; about 5% of the DNA) after fractionation and those of average size (5-15 kb) for content of some specific genes. We find that the largest molecules are not a representative sampling of the genome. Three contiguous genes located in a G+C-rich isochore (tyrosine hydroxylase, insulin, insulin-like growth factor II) have concentrations two to three times greater in the largest molecules. This shows that this genomic region has fewer pyrimidine dimers than most other genomic regions. In contrast, the β-actin genomic region, which has a similar G+C content, has an equal concentration in both fractions as do the p53 and β-globin genomic regions, which are A+T-rich. These data show that DNA damage in the form of cyclobutane pyrimidine dimers occurs with different probabilities in specific isochores. Part of the reason may be the relative G-C content, but other factors must play a significant role. We also report that the transcriptionally inactive insulin region is repaired at the genome-overall rate in normal cells and is not repaired in xeroderma pigmentosum complementation group C cells. (author)

  15. The EGF repeat-specific O-GlcNAc-transferase Eogt interacts with notch signaling and pyrimidine metabolism pathways in Drosophila.

    Reto Müller

    Full Text Available The O-GlcNAc transferase Eogt modifies EGF repeats in proteins that transit the secretory pathway, including Dumpy and Notch. In this paper, we show that the Notch ligands Delta and Serrate are also substrates of Eogt, that mutation of a putative UDP-GlcNAc binding DXD motif greatly reduces enzyme activity, and that Eogt and the cytoplasmic O-GlcNAc transferase Ogt have distinct substrates in Drosophila larvae. Loss of Eogt is larval lethal and disrupts Dumpy functions, but does not obviously perturb Notch signaling. To identify novel genetic interactions with eogt, we investigated dominant modification of wing blister formation caused by knock-down of eogt. Unexpectedly, heterozygosity for several members of the canonical Notch signaling pathway suppressed wing blister formation. And importantly, extensive genetic interactions with mutants in pyrimidine metabolism were identified. Removal of pyrimidine synthesis alleles suppressed wing blister formation, while removal of uracil catabolism alleles was synthetic lethal with eogt knock-down. Therefore, Eogt may regulate protein functions by O-GlcNAc modification of their EGF repeats, and cellular metabolism by affecting pyrimidine synthesis and catabolism. We propose that eogt knock-down in the wing leads to metabolic and signaling perturbations that increase cytosolic uracil levels, thereby causing wing blister formation.

  16. Synthesis and applications of selectively {sup 13}C-labeled RNA

    SantaLucia, J. Jr.; Shen, L.X.; Lewis, H.; Cai, Z.; Tinoci, I. Jr. [Univ. of California, Berkeley, CA (United States)

    1994-12-01

    Spectral overlap is a substantial problem in NMR studies of RNA molecules >30 nucleotides. To overcome this difficulty, we synthesized selectively {sup 13}C-labeled RNAs and adapted several isotope-edited two- and three-dimensional NMR experiments originally developed for protein studies. We optimized protocols for synthesis of multi-gram quantities of CTP, UTp, ATP, and GTP using a combination of synthetic organic and enzymatic methods. Uracil is prepared in 40 to 50% yield from {sup 13}C-cyanide in two steps. Using acetyl- tribenzoyl-ribose and standard chemistry uracil is then attached to the sugar (90% yield). The tribenzoyl-uridine intermediate is converted into uridine or cytidine quantitatively, depending on the deblocking protocol. Labeled purines are synthesized using simple pyrimidine precursors and reacting with {sup 13}C-formic acid (80% yield). Purine nucleosides are then synthesized using uridine phosphorylase and purine nucleoside phosphorylase. The nucleosides were converted to NMPs by treatment with POC1{sub 3} in triethylphosphate. We converted NMPs to NTPs by standard enzymatic methods. Selectively labeled RNAs were synthesized by run-off transcription using {sup 13}C-labeled NTPs. Several different strategies help solve over-lap problems in larger RNAs. Isotope-edited two-dimensional NMR experiments such as {omega}1-1/2 X-filtered NOESY simplify NMR spectra by dividing the normal NOESY spectrum into two subspectra-one involving NOEs from protons bound to {sup 12}C and one from protons bound to {sup 13}C. For example, we labeled A and U residues of a 34-nucleotide pseudoknot, and the {sup 12}C subspectrum of the 1/2 X-filtered NOESY contained NOEs only from G and C residues (along with adenine 2H); the {sup 13}C subspectrum contained NOEs only from A and U residues. Each subspectrum has less overlap than the NOESY of an unlabeled sample; the editing strategy allows each resonance to be identified by residue type (A, C, G, or U).

  17. A Facile Synthesis of 5'-Fluoro-5'-deoxyacadesine (5'-F-AICAR: A Novel Non-phosphorylable AICAR Analogue

    Luciano Mayol

    2012-11-01

    Full Text Available The substitution of a hydroxyl group by a fluorine atom in a potential drug is an efficient reaction that can, in principle, improve its pharmacological properties. Herein, the synthesis of the novel compound 5′-fluoro-5′-deoxyacadesine (5′-F-AICAR, a strict analogue of AICAR that cannot be 5′-phosphorylated to ZMP by cellular kinases, is reported.

  18. The labeling debate in the United States.

    Marchant, Gary E; Cardineau, Guy A

    2013-01-01

    The mandatory labeling of genetically modified (GM) food has become the predominant policy issue concerning biotechnology in the United States. The controversy over GM labeling is being debated at several different levels and branches of government. At the federal level, the Food and Drug Administration, which has primary jurisdiction over food safety and labeling, has steadfastly refused to require labeling of GM foods since 1992 based on its conclusion that GM foods as a category present no unique or higher risks than other foods. Proposed legislation has been repeatedly introduced in the US. Congress over the years to mandate GM labeling, but has made very little progress. With federal labeling requirements apparently stalled, the main activity has switched to the state level, where numerous individual states are considering mandatory GM labeling, either through legislation or proposition. The debate over GM labeling, at both the federal and state levels, has focused on five issues: (1) public opinion; (2) the legality of labeling requirements; (3) the risks and benefits of GM foods; (4) the costs and burdens of GM labeling; and (5) consumer choice. While the pro-labeling forces argue that all of these factors weigh in favor of mandatory GM labeling, a more careful evaluation of the evidence finds that all five factors weigh decisively against mandatory GM labeling requirements. PMID:23982076

  19. A Multi-Label Classification Approach Based on Correlations Among Labels

    Raed Alazaidah

    2015-02-01

    Full Text Available Multi label classification is concerned with learning from a set of instances that are associated with a set of labels, that is, an instance could be associated with multiple labels at the same time. This task occurs frequently in application areas like text categorization, multimedia classification, bioinformatics, protein function classification and semantic scene classification. Current multi-label classification methods could be divided into two categories. The first is called problem transformation methods, which transform multi-label classification problem into single label classification problem, and then apply any single label classifier to solve the problem. The second category is called algorithm adaptation methods, which adapt an existing single label classification algorithm to handle multi-label data. In this paper, we propose a multi-label classification approach based on correlations among labels that use both problem transformation methods and algorithm adaptation methods. The approach begins with transforming multi-label dataset into a single label dataset using least frequent label criteria, and then applies the PART algorithm on the transformed dataset. The output of the approach is multi-labels rules. The approach also tries to get benefit from positive correlations among labels using predictive Apriori algorithm. The proposed approach has been evaluated using two multi-label datasets named (Emotions and Yeast and three evaluation measures (Accuracy, Hamming Loss, and Harmonic Mean. The experiments showed that the proposed approach has a fair accuracy in comparison to other related methods.

  20. How to Read a Nutrition Facts Label

    Full Text Available ... Cerebral Palsy: Caring for Your Child All About Food Allergies How to Read a Nutrition Facts Label ( ... THIS TOPIC Keeping Portions Under Control Figuring Out Food Labels Healthy Food Shopping If My Child Has ...

  1. Preparation of 35S labelled thiosemicarbazone

    A 35S labelled thiosemicarbazone is prepared, on a millimole scale by reacting labelled thiocyanate with hydrazine sulfate in ethanolic medium. The hydrazine thiocyanate so formed is then condensed with aldehyde to form the thiosemicarbazone

  2. Preparation of methyl-3H labelled dimethylnitrosamine

    Tritium labelled dimethylamine was prepared from benzalmethylimine in reaction with methyl-3H iodide followed by hydrolysis. The product was converted with sodium nitrite in glacial acetic acid into labelled dimethylnitrosamine. The radiochemical yield was 85%. (author)

  3. Labelling schemes: From a consumer perspective

    Juhl, Hans Jørn; Stacey, Julia

    2000-01-01

    , their size etc. are studied before setting up a label scheme. A new labelling study was launched in 2000, the purpose of which is to: * improve the foundation for evaluating the value and effect of labelling schemes * improve the possibilities for pursuing an active consumer policy within the area * give......Labelling of food products attracts a lot of political attention these days. As a result of a number of food scandals, most European countries have acknowledged the need for more information and better protection of consumers. Labelling schemes are one way of informing and guiding consumers....... However, initiatives in relation to labelling schemes seldom take their point of departure in consumers' needs and expectations; and in many cases, the schemes are defined by the institutions guaranteeing the label. It is therefore interesting to study how consumers actually value labelling schemes...

  4. Ivabradine: A Review of Labeled and Off-Label Uses.

    Oliphant, Carrie S; Owens, Ryan E; Bolorunduro, Oluwaseyi B; Jha, Sunil K

    2016-10-01

    Ivabradine is a unique medication recently approved in the USA for the treatment of select heart failure patients. It was first approved for use in several countries around the world over a decade ago as an anti-anginal agent, with subsequent approval for use in heart failure patients. Since ivabradine has selective activity blocking the I f currents in the sinus node, it can reduce heart rate without appreciable effects on blood pressure. Given this heart-rate-specific effect, it has been investigated in many off-label indications as an alternative to traditional heart-rate-reducing medications such as beta blockers and calcium channel blockers. We conducted searches of PubMed and Google Scholar for ivabradine, heart failure, HFrEF, HFpEF, angina, coronary artery disease, inappropriate sinus tachycardia, postural orthostatic hypotension, coronary computed tomography angiography and atrial fibrillation. We reviewed and included studies, case reports, and case series published between 1980 and June 2016 if they provided information relevant to the practicing clinician. In many cases, larger clinical trials are needed to solidify the benefit of ivabradine, although studies indicate benefit in most therapeutic areas explored to date. The purpose of this paper is to review the current labeled and off-label uses of ivabradine, with a focus on clinical trial data. PMID:27405864

  5. 77 FR 12313 - Food Labeling Workshop; Public Workshop

    2012-02-29

    ..., (3) nutrition labeling requirements, (4) health and nutrition claims, and (5) special labeling issues... with labeling requirements, especially in light of growing concerns about obesity and food...

  6. Do Consumers Really Use Food Labels?

    Ward, Ronald W.; Jauregui, Carlos E.

    2006-01-01

    Ordered Probit models are used to estimate the probabilities of consumers reading food labels for harmful ingredients and for using labels to assist with food purchasing decisions. Demographics, health concerns, attitudes, and eating habits are shown to influence the likelihood of using food labels. Effects from over 25 variables are ranked in terms of their relative impacts on the use of food labels. Dieting, concerns about calories, foreign foods, and many other variable effects on the use ...

  7. 99mTc: Labeling Chemistry and Labeled Compounds

    Alberto, R.; Abram, U.

    This chapter reviews the radiopharmaceutical chemistry of technetium related to the synthesis of perfusion agents and to the labeling of receptor-binding biomolecules. To understand the limitations of technetium chemistry imposed by future application of the complexes in nuclear medicine, an introductory section analyzes the compulsory requirements to be considered when facing the incentive of introducing a novel radiopharmaceutical into the market. Requirements from chemistry, routine application, and market are discussed. In a subsequent section, commercially available 99mTc-based radiopharmaceuticals are treated. It covers the complexes in use for imaging the most important target organs such as heart, brain, or kidney. The commercially available radiopharmaceuticals fulfill the requirements outlined earlier and are discussed with this background. In a following section, the properties and perspectives of the different generations of radiopharmaceuticals are described in a general way, covering characteristics for perfusion agents and for receptor-specific molecules. Technetium chemistry for the synthesis of perfusion agents and the different labeling approaches for target-specific biomolecules are summarized. The review comprises a general introduction to the common approaches currently in use, employing the N x S4-x , [3+1] and 2-hydrazino-nicotinicacid (HYNIC) method as well as more recent strategies such as the carbonyl and the TcN approach. Direct labeling without the need of a bifunctional chelator is briefly reviewed as well. More particularly, recent developments in the labeling of concrete targeting molecules, the second generation of radiopharmaceuticals, is then discussed and prominent examples with antibodies/peptides, neuroreceptor targeting small molecules, myocardial imaging agents, vitamins, thymidine, and complexes relevant to multidrug resistance are given. In addition, a new approach toward peptide drug development is described. The section

  8. How to Read a Nutrition Facts Label

    Full Text Available ... Cerebral Palsy: Caring for Your Child All About Food Allergies How to Read a Nutrition Facts Label (Video) KidsHealth > For Parents > How to Read a Nutrition Facts Label (Video) Print A A A Text Size ... MORE ON THIS TOPIC Keeping Portions Under Control Figuring Out Food Labels Healthy Food Shopping If My Child Has ...

  9. 40 CFR 211.105 - Label format.

    2010-07-01

    ... 40 Protection of Environment 24 2010-07-01 2010-07-01 false Label format. 211.105 Section 211.105 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) NOISE ABATEMENT PROGRAMS PRODUCT NOISE LABELING General Provisions § 211.105 Label format. (a) Unless specified otherwise in other...

  10. 21 CFR 701.11 - Identity labeling.

    2010-04-01

    ... 21 Food and Drugs 7 2010-04-01 2010-04-01 false Identity labeling. 701.11 Section 701.11 Food and... COSMETIC LABELING Package Form § 701.11 Identity labeling. (a) The principal display panel of a cosmetic in package form shall bear as one of its principal features a statement of the identity of the commodity....

  11. What determines consumer attention to nutrition labels?

    Bialkova, S.E.; Trijp, van J.C.M.

    2010-01-01

    To identify the key determinants of consumer attention to nutrition labels, visual search tasks (present – absent; one – two targets) were used as an effective experimental tool. The main manipulation concerned: set size (number of labels on front of pack); label characteristics (display size, posit

  12. 21 CFR 225.80 - Labeling.

    2010-04-01

    ... CURRENT GOOD MANUFACTURING PRACTICE FOR MEDICATED FEEDS Packaging and Labeling § 225.80 Labeling. (a... adhered to, will assure that the article is safe and effective for its intended purposes. (b)(1) Labels... medicated feed and includes adequate information for the safe and effective use of the medicated feed....

  13. 21 CFR 1271.250 - Labeling controls.

    2010-04-01

    ...) General. You must establish and maintain procedures to control the labeling of HCT/Ps. You must design these procedures to ensure proper HCT/P identification and to prevent mix-ups. (b) Verification.... Procedures must ensure that each HCT/P is labeled in accordance with all applicable labeling...

  14. Evaluation of radioprotective efficacy of pyrimidine-5- carboxylate derivative on electron beam induced oxidative stress using Drosophila Melanogaster

    Protection of biological systems against radiation damage is of paramount importance during accidental and unavoidable exposure to radiation. Several physico-chemical and biological factors collectively contribute to the damage caused by radiation and are, therefore, targets for developing radioprotectors. Chemicals capable of scavenging free radicals, inducing oxygen depletion, ant ioxidants and modulators of immune response have been some of the radioprotectors extensively investigated with limited success. In the present study the radioprotective efficacy of Ethyl 4-(4-(benzyloxy)phenyl)-6-methyl-2-oxo-1,2,3,4-tetrahydro pyrimidine-5-carboxylate on electron beam induced oxidative stress was evaluated using Drosophila melanogaster (Oregon K). Initially the molecule was tested for in vitro antioxidant activity and it showed moderate DPPH radical scavenging activity and good hydroxyl radical scavenging activity compared to standard glutathione. Hence, this compound was screened for its radioprotective activity. The compound was supplied to flies in the form of diet. The electron beam irradiated flies were assayed for oxidative stress markers name Thiobarbituric acid reactive substances (TBARS), enzymatic and Non-enzymatic antioxidants. The pyrimidinone showed modulator effect on the oxidative stress markers caused by e-beam radiation. (author)

  15. Design and synthesis of some substituted thiazolo[3,2-a]pyrimidine derivatives of potential biological activities

    Samia G. Abdel Moty

    2016-03-01

    Full Text Available In continuation to our previous work, thiazolopyrimidines 2a–x were synthesized through intramolecular cyclization of 2-phenacylthio-dihydropyrimidine hydrobromides 1a–x using polyphosphoric acid. On the other hand, thiazolo[3,2-a]pyrimidine-3-one 3 was coupled with aryldiazonium salts or condensed with isatin to afford compounds 4a–c or 5, respectively. Chemical structure of the target compounds was substantiated by IR, FT-IR, 1H-, 13C and DEPT-13C NMR, MS as well as microanalyses. Moreover, the lipophilicity of the target compounds is expressed as ClogP. The antimicrobial screening of the test compounds 2a–x, 4a–c and 5 revealed moderate activity in comparison to reference drugs. Compounds 2a–c, 2e, 2o and 2v showed a gradual increase in their anti-inflammatory activity reaching its maximum at 5 h compared to indomethacin. Furthermore, the analgesic activity of compounds 2a–c, 2e, 2o and 2v revealed a maximum activity after 5 h of injection compared to aspirin and the LD50 of compounds 2e and 2v was determined.

  16. Ultraviolet-B sensitivities in Japanese lowland rice [Oryza sativa] cultivars: Cyclobutane pyrimidine dimer photolyase activity and gene mutation

    There is a cultivar difference in the response to ultraviolet-B (UVB: 280-320 um) in rice (Oryza saliva L.). Among Japanese lowland rice cultivars, Sasanishiki, a leading Japanese rice cultivar, is resistant to the damaging effects of UVB while Norin 1, a close relative, is less resistant. We found previously that Norin 1 was deficient in cyclobutane pyrimidine dimer (CPD) photorepair ability and suggested that the UVB sensitivity in rice depends largely on CPD photorepair ability. In order to verify that suggestion, we examined the correlation between UVB sensitivity and CPD photolyase activity in 17 rice cultivars of progenitors and relatives in breeding of UV-resistant Sasanishiki and UV- sensitive Norin 1. The amino acid at position 126 of the deduced amino acid sequence of CPD photolyase in cultivars including such as Norin 1 was found to be arginine, the CPD photolyase activities of which were lower. The amino acid at that position in cultivars including such as Sasanishiki was glutamine. Furthermore, cultivars more resistant to UVB were found to exhibit higher photolyase activities than less resistant cultivars. These results emphasize that single amino acid alteration from glutamine to arginine leads to a deficit of CPD photolyase activity and that CPD photolyase activity is one of the main factors determining UVB sensitivity in rice

  17. Design and synthesis of some substituted thiazolo[3,2-a]pyrimidine derivatives of potential biological activities.

    Abdel Moty, Samia G; Hussein, Mostafa A; Abdel Aziz, Salah A; Abou-Salim, Mahrous A

    2016-03-01

    In continuation to our previous work, thiazolopyrimidines 2a-x were synthesized through intramolecular cyclization of 2-phenacylthio-dihydropyrimidine hydrobromides 1a-x using polyphosphoric acid. On the other hand, thiazolo[3,2-a]pyrimidine-3-one 3 was coupled with aryldiazonium salts or condensed with isatin to afford compounds 4a-c or 5, respectively. Chemical structure of the target compounds was substantiated by IR, FT-IR, (1)H-, (13)C and DEPT-(13)C NMR, MS as well as microanalyses. Moreover, the lipophilicity of the target compounds is expressed as Clog P. The antimicrobial screening of the test compounds 2a-x, 4a-c and 5 revealed moderate activity in comparison to reference drugs. Compounds 2a-c, 2e, 2o and 2v showed a gradual increase in their anti-inflammatory activity reaching its maximum at 5 h compared to indomethacin. Furthermore, the analgesic activity of compounds 2a-c, 2e, 2o and 2v revealed a maximum activity after 5 h of injection compared to aspirin and the LD50 of compounds 2e and 2v was determined. PMID:27013904

  18. High hRFI expression correlates with resistance to Fluoro pyrimidines in human colon cancer cell lines and in xenografts

    We previously reported that the over-expression of hRFI, a protein preferentially expressed in the digestive tract regions of several cancers, exhibited a tendency to inhibit TNF-α induced apoptosis. In this study, we sought to determine the potential effect of hRFI expression on the sensitivity to 5-fluorouracil (5-FU) and/or other fluoro pyrimidines. For the whole lysates of 8 colon cancer cell lines, we performed Western blotting with anti-hRFI antibody and analyzed the correlations between the expression level of hRFI and the cell lines' sensitivity to 5-FU induced apoptosis. Furthermore, for a tissue micro array consisting of 32 xenograft derived human cancer cell lines, we examined the expression levels of hRFI and survivin by immunohistochemical staining, and analyzed the correlations between the expression of each protein and the sensitivity to several chemotherapeutic agents in the xenografts examined. Both in colon cancer cell lines and in xenografts, the expression level of hRFI was correlated with resistance to 5-FU and its derivatives. This evidence suggests that hRFI may be a marker predicting the response to fluorouracil derived chemotherapeutic agents and that the reduction of the expression level of hRFI might improve the outcome of chemotherapy

  19. Preparation,Crystal Structure and Theoretical Calculation of N-(Pyrimidin-2-yl)-N'-methoxycarbonyl-thiourea

    REN,Ying-Hui; SONG,Ji-Rong; XU,Kang-Zhen; MA,Hai-Xia; HUANG,Jie; FU,Ding-Wei; HU,Huai-Ming

    2007-01-01

    The compound,N-(pyrimidin-2-yl)-N'-methoxycarbonyl-thiourea,has been synthesized.The single crystal structure has been determined by an X-ray diffractometer.The crystal belongs to triclinic with space group P-1 and a=0.72152(4)nm,b=0.8056(4)nm,c=0.90772(5)nm,α=105.141(4).,B=94.588(4).,γ=115.415(4).,F(000)=220,the unit cell volume V=0.45704(4)nm3,the molecule number in one unit cell Z=2,the absorption coefficient μ=0.333 mm-1,the calculated density Dc=1.542 g/cm3.The theoretical investigation of the title compound was carded out with B3L YP/6-311G.HF/6-311G and MP2/6-311G methods,and the atomic charges and natural bond orbital analysis were also discussed.

  20. In vivo protective effect of Uridine, a pyrimidine nucleoside, on genotoxicity induced by Levodopa/Carbidopa in mice.

    Orenlili Yaylagul, Esra; Cansev, Mehmet; Celikler Kasimogullari, Serap

    2015-08-01

    Parkinson's disease (PD) is a common neurodegenerative disorder that affects millions of people all over the world. Motor symptoms of PD are most commonly controlled by L-3,4-dihydroxyphenylalanine (Levodopa, L-DOPA), a precursor of dopamine, plus a peripherally-acting aromatic-L-amino-acid decarboxylase (dopa decarboxylase) inhibitor, such as carbidopa. However, chronic treatment with a combination of Levodopa plus carbidopa has been demonstrated to cause a major complication, namely abnormal involuntary movements. On the other hand, the effect of this treatment on bone marrow cells is unknown. Therefore, in this study, we aimed to investigate possible genotoxic effects of Levodopa and Carbidopa using male Balb/C mice. Our results showed that Levodopa alone or in combination with carbidopa caused genotoxicity in in vivo micronucleus test (mouse bone marrow) and Comet assay (blood cells). Furthermore, we showed that simultaneous administration of uridine, a pyrimidine nucleoside, reversed the genotoxic effect of Levodopa and Carbidopa in both assays. Our data show for the first time that Levodopa plus carbidopa combination causes genotoxicity which is reversed by uridine treatment. These findings might enhance our understanding for the complications of a common Parkinson's treatment and confer benefit in terms of reducing a possible genotoxic effect of this treatment. PMID:25976300

  1. 7-Methyl-5,6,7,8-tetrahydro-1-benzothieno[2,3-d]pyrimidin-4-amine

    Mohamed Ziaulla

    2011-07-01

    Full Text Available In the title compound, C11H13N3S, two of the C atoms of the cyclohexene ring and the methyl group attached to it are disordered over two sets of sites in a 0.544 (2:0.456 (2 ratio. The benzothiene and pyrimidine rings are almost coplanar with an angular tilt of 2.371 (9° between them. The thiophene ring is essentially planar (r.m.s. deviation 0.05 Å, while the cyclohexene ring in both the major- and minor-occupancy conformers adopts a half-chair conformation. In the crystal structure, pairs of intermolecular N—H...N hydrogen bonds involving the amino groups result in centrosymmetric head-to-head dimers about inversion centres, corresponding to an R22(8 graph-set motif. Further, N—H...N hydrogen bonding generates a two-dimensional hydrogen-bonded network perpendicular to the ac plane and running along the diagonal of the ac plane.

  2. An unidentified ultraviolet-B-specific photoreceptor mediates transcriptional activation of the cyclobutane pyrimidine dimer photolyase gene in plants.

    Ioki, Motohide; Takahashi, Shinya; Nakajima, Nobuyoshi; Fujikura, Kohei; Tamaoki, Masanori; Saji, Hikaru; Kubo, Akihiro; Aono, Mitsuko; Kanna, Machi; Ogawa, Daisuke; Fukazawa, Jutarou; Oda, Yoshihisa; Yoshida, Seiji; Watanabe, Masakatsu; Hasezawa, Seiichiro; Kondo, Noriaki

    2008-12-01

    Cyclobutane pyrimidine dimers (CPDs) constitute a majority of DNA lesions caused by ultraviolet-B (UVB). CPD photolyase, which rapidly repairs CPDs, is essential for plant survival under sunlight containing UVB. Our earlier results that the transcription of the cucumber CPD photolyase gene (CsPHR) was activated by light have prompted us to propose that this light-driven transcriptional activation would allow plants to meet the need of the photolyase activity upon challenges of UVB from sunlight. However, molecular mechanisms underlying the light-dependent transcriptional activation of CsPHR were unknown. In order to understand spectroscopic aspects of the plant response, we investigated the wavelength-dependence (action spectra) of the light-dependent transcriptional activation of CsPHR. In both cucumber seedlings and transgenic Arabidopsis seedlings expressing reporter genes under the control of the CsPHR promoter, the action spectra exhibited the most predominant peak in the long-wavelength UVB waveband (around 310 nm). In addition, a 95-bp cis-acting region in the CsPHR promoter was identified to be essential for the UVB-driven transcriptional activation of CsPHR. Thus, we concluded that the photoperception of long-wavelength UVB by UVB photoreceptor(s) led to the induction of the CsPHR transcription via a conserved cis-acting element. PMID:18825406

  3. Pyrimidine dimer induction and repair in cultured human skin keratinocytes or melanocytes after irradiation with monochromatic ultraviolet radiation

    We compared the susceptibilities of cultured melanocytes and keratinocytes to dimer induction in DNA by monochromatic ultraviolet (UV) radiation. Keratinocytes as well as melanocytes were derived from human foreskin, grown as a monolayer in petri dishes, covered with phosphate-buffered saline containing 0.1% glucose, and irradiated. UV irradiation was carried out at 254, 297, and 302 nm as well as with a light source emitting predominantly 312 nm. The induction of pyrmidine dimers was assessed by determination of the number of T4 endonuclease V-sensitive sites (ESS). We found a slightly higher response for dimer induction in melanocytes at 254, 297, and 302 nm; this difference was only significant at the 297-nm wavelength. Action spectra for pyrimidine dimer induction were derived from the exposure-response data obtained. The action spectra mimic to a large degree the action spectra for dimer induction in other cultured mammalian cells. The repair rate during a post-irradiation period lasting up to 24 h was substantially the same for the two cell types. The percentage of T4 endonuclease V-sensitive sites (ESS) remaining 9 and 24 h after irradiation was 45% and 30%, respectively

  4. 201Tl labelled myocardium tomoscanning

    A new device, the J and P Tomoscanner, enables us to obtain the transverse scintigraphic section of any organ labelled by a single photon emitting radionuclide. For the time being, this technique has been used mainly for brain and liver studies. This work explores the ability of this tomograph to furnish sections of the 201Tl labelled myocardium by comparing them with the scintillation gamma-camera images. Towards this aim, witnesses and patients with documented anterior or lateral infarctus have been studied. Our actual results show a high correlation between the two explorations. But, by means of the section, both the site and size of the necrosis are visualized. However, only a single tomographic image was obtained in each patient because of the time necessary for its retranscription on paper. In the near future, when it will be possible to perform routinely several sections, a better size estimation will be possible

  5. Pharmaceuticals labelled with stable isotopes

    The relatively new field of pharmaceuticals labelled with stable isotopes is reviewed. Scientific, juridical, and ethical questions are discussed concerning the application of these pharmaceuticals in human medicine. 13C, 15N, and 2H are the stable isotopes mainly utilized in metabolic function tests. Methodical contributions are given to the application of 2H, 13C, and 15N pharmaceuticals showing new aspects and different states of development in the field under discussion. (author)

  6. Radioactively labelled vitamin B12

    A method is described for preparing radioactively labelled vitamin B 12 (cyanocobalamin) by reacting α-(5,6-dimethylbenzimidazolyl) hydrogenobamide with active (sup(57,58)Co) cobaltous ion. The latter may be in the form of cobaltous chloride or sulphate in aqueous or aqueous alcoholic medium. The reaction is effected by heating the reactants in darkness at pH 4 to 8. An excess of cyanide is added to convert the hydroxocobalamin formed to cyanocobalamin. (U.K.)

  7. Biomolecule labelling by 186 Re

    The aim of this study is to develop and improve the existing radiolabelling techniques of peptides and monoclonal antibodies with 186 Re and 188 Re as potential agents for cancer targeted radiotherapy. We selected the following methods and techniques for direct labelling of peptides and monoclonal antibody: 1. Prereduction of -S-S- bridges of biomolecule to sulfhydryls using reducing agents: ascorbic acid, cysteine, active hydrogen, 2,3 dimercaptopropanol. The prereduction reactions are controlled by massic ratios of reduction agents/biomolecule, pH, temperature and time of incubation; 2. Reduction of 186 Re O4- stannous chloride in acid and alkaline pH; 3. Coupling reaction of 186 Re (red) with the biomolecule controlled by the time and temperature of incubation, the influence of pH regarding the binding of 186 Re to the biomolecules. The quality control was effected by chromatography techniques (paper and elution gel chromatography) on labeled biomolecule before and after purification. The elution gel chromatography was spectrophotometricaly monitored at 280 nm. In the same time the radioactivity of samples was measured using a gamma counter. All the results confirm in vitro stability of labeled biomolecule. The biological evaluation studies regarding accumulation and biological affinity will be controlled by scintigraphy method. Biodistribution studies will be effected to Walker tumor bearing animals at 4 and 24 hours after injections. (authors)

  8. Use of Symbols in Labeling. Final rule.

    2016-06-15

    The Food and Drug Administration (FDA or the Agency) is issuing this final rule revising its medical device and certain biological product labeling regulations to explicitly allow for the optional inclusion of graphical representations of information, or symbols, in labeling (including labels) without adjacent explanatory text (referred to in this document as "stand-alone symbols") if certain requirements are met. The final rule also specifies that the use of symbols, accompanied by adjacent explanatory text continues to be permitted. FDA is also revising its prescription device labeling regulations to allow the use of the symbol statement "Rx only" or "[rx] only" in the labeling for prescription devices. PMID:27311137

  9. Eye tracking and nutrition label use

    Graham, Dan J.; Orquin, Jacob Lund; Visschers, Vivianne H.M.

    2012-01-01

    cameras monitoring consumer visual attention (i.e., eye tracking) has begun to identify ways in which label design could be modified to improve consumers’ ability to locate and effectively utilize nutrition information. The present paper reviews all published studies of nutrition label use that have......Nutrition labels on food packages are among the most prominent and far-reaching policy measures related to diet and have the capacity to promote healthy eating. Unfortunately, certain nutrition label characteristics may impede consumer detection and comprehension of labels. Research using precise...

  10. The economics of GM food labels: An evaluation of mandatory labeling proposals in India

    Bansal, Sangeeta; Ramaswami, Bharat

    2007-01-01

    "Labeling of genetically modified (GM) foods is a contentious issue and internationally, there is sharp division whether such labeling ought to be mandatory. This debate has reached India where the government has proposed mandatory labeling. In this context, this paper evaluates the optimal regulatory approach to GM food labels. Mandatory labeling aims to provide greater information and correspondingly more informed consumer choice. However, even without such laws, markets have incentives to ...

  11. Modulating the Cyclic Guanosine Monophosphate Substrate Selectivity of the Phosphodiesterase 3 Inhibitors by Pyridine, Pyrido[2,3-d]pyrimidine Derivatives and Their Effects upon the Growth of HT-29 Cancer Cell Line

    Abadi, Ashraf Hassan; Hany, Marwa Saeed; Elsharif, Shimaa Awadain; Eissa, Amal Abdel Haleem; Gary, Bernard DeWayne; Tinsley, Heather Nicole; Piazza, Gary Anthony

    2016-01-01

    Analogues with the scaffolds of 3-cyano-4-alkoxyphenyl-6-bromoaryl-2-pyridone and 2-amino-3-cyano-4-alkoxyphenyl-6-bromoarylpyridine were synthesized. Cyclization of the 2-amino derivatives with formic acid and formamide gave the corresponding pyrido[2,3-d]pyrimidin-4(3H)-one and the pyrido[2,3-d]pyrimidin-4-amine derivatives, respectively. Active phosphodiesterase 3 (PDE3) inhibitors were identified from each of the four aforementioned scaffolds. This is the first report that pyrido[2,3-d]pyrimidin-4(3H)-one and pyrido[2,3-d]pyrimidin-4-amine derivatives can inhibit PDE3. The analogues with the pyridone and pyrido[2,3-d]pyrimidin-4(3H)-one scaffolds inhibited both cAMP and cyclic guanosine monophosphate (cGMP) hydrolysis by PDE3, while the amine containing scaffolds were more selective for cGMP hydrolysis. This observation may set the base for substrate-selective pharmacological modulation of this important class of drug targets and with less side effects, particularly tachcardia. The dual inhibitors of PDE3 were more potent inhibitor towards the growth of HT-29 cancer cell lines. PMID:23546000

  12. Fluorescent labeling and tracking of nanoclay

    Diaz, Carlos A.; Xia, Yining; Rubino, Maria; Auras, Rafael; Jayaraman, Krishnamurthy; Hotchkiss, Joseph

    2012-12-01

    We report a methodology developed to detect and track stable fluorescent-labeled nanoclay, in polymer-clay nanocomposite films, and in a contact solvent after migration testing. Fluorescein-5-maleimide (fluorescein) or tetramethylrhodamine-5-maleimide (rhodamine) was covalently bonded to organically modified montmorillonite (o-MMT). Fluorescein- and rhodamine-labeled nanoclay showed good thermal stability up to 220 °C and the rhodamine-labeled nanoclay remained stable at 250 °C. Confocal laser scanning microscopy was used to confirm the tagging and to detect the fluorescent-labeled nanoclays in various systems.We report a methodology developed to detect and track stable fluorescent-labeled nanoclay, in polymer-clay nanocomposite films, and in a contact solvent after migration testing. Fluorescein-5-maleimide (fluorescein) or tetramethylrhodamine-5-maleimide (rhodamine) was covalently bonded to organically modified montmorillonite (o-MMT). Fluorescein- and rhodamine-labeled nanoclay showed good thermal stability up to 220 °C and the rhodamine-labeled nanoclay remained stable at 250 °C. Confocal laser scanning microscopy was used to confirm the tagging and to detect the fluorescent-labeled nanoclays in various systems. Electronic supplementary information (ESI) available: Additional information regarding production of nanocomposites, the silylation procedure, labeling of the nanoclays, characterization of the labels, thermal stability of the labels, and the migration test. See DOI: 10.1039/c2nr32978f

  13. 75 FR 29775 - Food Labeling Workshop; Public Workshop

    2010-05-27

    ... be discussed at the workshop include: (1) Mandatory label elements, (2) nutrition labeling... labeling and nutrition. FDA expects that participation in this public workshop will provide regulated... with labeling requirements, especially in light of growing concerns about obesity and food...

  14. Dengue virus growth, purification, and fluorescent labeling.

    Zhang, Summer; Chan, Kuan Rong; Tan, Hwee Cheng; Ooi, Eng Eong

    2014-01-01

    The early events of the dengue virus life cycle involve virus binding, internalization, trafficking, and fusion. Fluorescently labeled viruses can be used to visualize these early processes. As dengue virus has 180 identical copies of the envelope protein attached to the membrane surface and is surrounded by a lipid membrane, amine-reactive (Alexa Fluor) or lipophilic (DiD) dyes can be used for virus labeling. These dyes are highly photostable and are ideal for studies involving cellular uptake and endosomal transport. To improve virus labeling efficiency and minimize the nonspecific labeling of nonviral proteins, virus concentration and purification precede fluorescent labeling of dengue viruses. Besides using these viruses for single-particle tracking, DiD-labeled viruses can also be used to distinguish serotype-specific from cross-neutralizing antibodies. Here the details of virus concentration, purification, virus labeling, applications, and hints of troubleshooting are described. PMID:24696327

  15. On randomized online labeling with polynomially many labels

    Bulánek, Jan; Koucký, Michal; Saks, M.

    Berlin: Springer, 2013 - (Fomin, F.; Freivalds, R.; Kwiatkowska, M.; Peleg, D.), s. 291-302. (Lecture Notes in Computer Science. 7965). ISBN 978-3-642-39205-4. [International Colloquium, ICALP 2013 /40./. Riga (LT), 08.07.2013-12.07.2013] R&D Projects: GA AV ČR IAA100190902; GA ČR GBP202/12/G061 Institutional support: RVO:67985840 Keywords : online labeling * complexity Subject RIV: BA - General Mathematics http://link.springer.com/chapter/10.1007%2F978-3-642-39206-1_25

  16. Hemoglobin Labeled by Radioactive Lysine

    Bale, W. F.; Yuile, C. L.; DeLaVergne, L.; Miller, L. L.; Whipple, G. H.

    1949-12-08

    This paper reports on the utilization of tagged epsilon carbon of DL-lysine by a dog both anemic and hypoproteinemic due to repeated bleeding plus a diet low in protein. The experiment extended over period of 234 days, a time sufficient to indicate an erythrocyte life span of at least 115 days based upon the rate of replacement of labeled red cell proteins. The proteins of broken down red cells seem not to be used with any great preference for the synthesis of new hemoglobin.

  17. Discovery of a SAR11 growth requirement for thiamin's pyrimidine precursor and its distribution in the Sargasso Sea.

    Carini, Paul; Campbell, Emily O; Morré, Jeff; Sañudo-Wilhelmy, Sergio A; Thrash, J Cameron; Bennett, Samuel E; Temperton, Ben; Begley, Tadhg; Giovannoni, Stephen J

    2014-08-01

    Vitamin traffic, the production of organic growth factors by some microbial community members and their use by other taxa, is being scrutinized as a potential explanation for the variation and highly connected behavior observed in ocean plankton by community network analysis. Thiamin (vitamin B1), a cofactor in many essential biochemical reactions that modify carbon-carbon bonds of organic compounds, is distributed in complex patterns at subpicomolar concentrations in the marine surface layer (0-300 m). Sequenced genomes from organisms belonging to the abundant and ubiquitous SAR11 clade of marine chemoheterotrophic bacteria contain genes coding for a complete thiamin biosynthetic pathway, except for thiC, encoding the 4-amino-5-hydroxymethyl-2-methylpyrimidine (HMP) synthase, which is required for de novo synthesis of thiamin's pyrimidine moiety. Here we demonstrate that the SAR11 isolate 'Candidatus Pelagibacter ubique', strain HTCC1062, is auxotrophic for the thiamin precursor HMP, and cannot use exogenous thiamin for growth. In culture, strain HTCC1062 required 0.7 zeptomoles per cell (ca. 400 HMP molecules per cell). Measurements of dissolved HMP in the Sargasso Sea surface layer showed that HMP ranged from undetectable (detection limit: 2.4 pM) to 35.7 pM, with maximum concentrations coincident with the deep chlorophyll maximum. In culture, some marine cyanobacteria, microalgae and bacteria exuded HMP, and in the Western Sargasso Sea, HMP profiles changed between the morning and evening, suggesting a dynamic biological flux from producers to consumers. PMID:24781899

  18. Rapid deamination of cyclobutane pyrimidine dimer photoproducts at TCG sites in a translationally and rotationally positioned nucleosome in vivo.

    Cannistraro, Vincent J; Pondugula, Santhi; Song, Qian; Taylor, John-Stephen

    2015-10-30

    Sunlight-induced C to T mutation hot spots in skin cancers occur primarily at methylated CpG sites that coincide with sites of UV-induced cyclobutane pyrimidine dimer (CPD) formation. The C and 5-methyl-C in CPDs are not stable and deaminate to U and T, respectively, which leads to the insertion of A by the DNA damage bypass polymerase η, thereby defining a probable mechanism for the origin of UV-induced C to T mutations. Deamination rates for T(m)CG CPDs have been found to vary 12-fold with rotational position in a nucleosome in vitro. To determine the influence of nucleosome structure on deamination rates in vivo, we determined the deamination rates of CPDs at TCG sites in a stably positioned nucleosome within the FOS promoter in HeLa cells. A procedure for in vivo hydroxyl radical footprinting with Fe-EDTA was developed, and, together with results from a cytosine methylation protection assay, we determined the translational and rotational positions of the TCG sites. Consistent with the in vitro observations, deamination was slower for one CPD located at an intermediate rotational position compared with two other sites located at outside positions, and all were much faster than for CPDs at non-TCG sites. Photoproduct formation was also highly suppressed at one site, possibly due to its interaction with a histone tail. Thus, it was shown that CPDs of TCG sites deaminate the fastest in vivo and that nucleosomes can modulate both their formation and deamination, which could contribute to the UV mutation hot spots and cold spots. PMID:26354431

  19. Pyrimidine Pool Disequilibrium Induced by a Cytidine Deaminase Deficiency Inhibits PARP-1 Activity, Leading to the Under Replication of DNA.

    Simon Gemble

    2015-07-01

    Full Text Available Genome stability is jeopardized by imbalances of the dNTP pool; such imbalances affect the rate of fork progression. For example, cytidine deaminase (CDA deficiency leads to an excess of dCTP, slowing the replication fork. We describe here a novel mechanism by which pyrimidine pool disequilibrium compromises the completion of replication and chromosome segregation: the intracellular accumulation of dCTP inhibits PARP-1 activity. CDA deficiency results in incomplete DNA replication when cells enter mitosis, leading to the formation of ultrafine anaphase bridges between sister-chromatids at "difficult-to-replicate" sites such as centromeres and fragile sites. Using molecular combing, electron microscopy and a sensitive assay involving cell imaging to quantify steady-state PAR levels, we found that DNA replication was unsuccessful due to the partial inhibition of basal PARP-1 activity, rather than slower fork speed. The stimulation of PARP-1 activity in CDA-deficient cells restores replication and, thus, chromosome segregation. Moreover, increasing intracellular dCTP levels generates under-replication-induced sister-chromatid bridges as efficiently as PARP-1 knockdown. These results have direct implications for Bloom syndrome (BS, a rare genetic disease combining susceptibility to cancer and genomic instability. BS results from mutation of the BLM gene, encoding BLM, a RecQ 3'-5' DNA helicase, a deficiency of which leads to CDA downregulation. BS cells thus have a CDA defect, resulting in a high frequency of ultrafine anaphase bridges due entirely to dCTP-dependent PARP-1 inhibition and independent of BLM status. Our study describes previously unknown pathological consequences of the distortion of dNTP pools and reveals an unexpected role for PARP-1 in preventing DNA under-replication and chromosome segregation defects.

  20. Wavelength dependence of pyrimidine dimer formation in DNA of human skin irradiated in situ with ultraviolet light

    The UV components of sunlight are believed to be a major cause of human skin caner, and DNA is though to be the principal molecular target. Alterations of the intensity and wavelength distribution of solar UV radiation reaching the surface of the earth, for example by depletion of stratospheric ozone, will change the effectiveness of solar radiation in damaging DNA in human skin. Evaluation of the magnitude of such effects requires knowledge of the altered sunlight spectrum and of the action spectrum for damaging DNA in human skin. The authors have determined an action spectrum for the frequency of pyrimidine dimer formation induced in the DNA of human skin per unit dose of UV incident on the skin surface. The peak of this action spectrum is near 300 nm and decreases rapidly at both longer and shorter wavelengths. The decrease in the action spectrum for wavelengths <300 nm is attributed to the absorption of the upper layers of the skin. Convolution of the dimer action spectrum with the solar spectra corresponding to a solar angle of 40 degree under current levels of stratospheric ozone and those for 50% ozone depletion, indicate about a 2.5-fold increase in dimer formation. If the action spectrum for DNA damage that results in skin cancer resembles that for dimer induction in skin, these results suggest that a 50% decrease in stratospheric ozone would increase the incidence of nonmelanoma skin cancers among white males in Seattle, Washington, by 7.5- to 8-fold, to a higher incidence than is presently seen in the corresponding population of Albuquerque, New Mexico