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Sample records for 5-fluoro pyrimidines labels

  1. 3'-O-(5-fluoro-2,4-dinitrophenyl)ADP ether and ATP ether. Affinity reagents for labeling ATPases.

    Science.gov (United States)

    Chuan, H; Wang, J H

    1988-09-15

    The affinity reagents 3'-O-(5-fluoro-2,4-dinitrophenyl)ADP ether (FDNP-ADP) and 3'-O-(5-fluoro-2,4-dinitrophenyl)ATP ether (FDNP-ATP) were synthesized and characterized. FDNP[14C]ADP was found to label the active site of mitochondrial F1-ATPase slowly at room temperature but with high specificity. F1 was effectively protected from the labeling reagent by ATP or ADP. An average number of 1.3 covalent label per F1 is sufficient for 100% inhibition of the ATPase. About 73% of the radioactive label was found covalently attached to beta subunits, 9% on alpha, practically none on gamma, delta, and epsilon. Cleavage of the labeled enzyme by pepsin and sequencing of the major radioactive peptide showed that the labeled amino acid residue in beta subunit was Lys beta 162. These results show that Lys beta 162 is indeed at the active site of F1 as assumed in the recently proposed models (Fry, D. C., Kuby, S. A., and Mildvan, A. S. (1986) Proc. Natl. Acad. Sci. U. S. A. 83, 907-911; Duncan, I. M., Parsonage, D., and Senior, A. E. (1986) FEBS Lett. 208, 1-6).

  2. Substituted Imidazole of 5-Fluoro-2-[4-[(2-phenyl-1H-imidazol-5-yl)methyl]-1-piperazinyl]pyrimidine Inactivates Cytochrome P450 2D6 by Protein Adduction

    Science.gov (United States)

    Nagy, Leslie D.; Mocny, Catherine S.; Diffenderfer, Laura E.; Hsi, David J.; Butler, Brendan F.; Arthur, Evan J.; Fletke, Kyle J.; Palamanda, Jairam R.; Nomeir, Amin A.

    2011-01-01

    5-Fluoro-2-[4-[(2-phenyl-1H-imidazol-5-yl)methyl]-1-piperazinyl]pyrimidine (SCH 66712) is a potent mechanism-based inactivator of human cytochrome P450 2D6 that displays type I binding spectra with a Ks of 0.39 ± 0.10 μM. The partition ratio is ∼3, indicating potent inactivation that addition of exogenous nucleophiles does not prevent. Within 15 min of incubation with SCH 66712 and NADPH, ∼90% of CYP2D6 activity is lost with only ∼20% loss in ability to bind CO and ∼25% loss of native heme over the same time. The stoichiometry of binding to the protein was 1.2:1. SDS-polyacrylamide gel electrophoresis with Western blotting and autoradiography analyses of CYP2D6 after incubations with radiolabeled SCH 66712 further support the presence of a protein adduct. Metabolites of SCH 66712 detected by mass spectrometry indicate that the phenyl group on the imidazole ring of SCH 66712 is one site of oxidation by CYP2D6 and could lead to methylene quinone formation. Three other metabolites were also observed. For understanding the metabolic pathway that leads to CYP2D6 inactivation, metabolism studies with CYP2C9 and CYP2C19 were performed because neither of these enzymes is significantly inhibited by SCH 66712. The metabolites formed by CYP2C9 and CYP2C19 are the same as those seen with CYP2D6, although in different abundance. Modeling studies with CYP2D6 revealed potential roles of various active site residues in the oxidation of SCH 66712 and inactivation of CYP2D6 and showed that the phenyl group of SCH 66712 is positioned at 2.2 Å from the heme iron. PMID:21422192

  3. The identification of 5'-fluoro-5-deoxyinosine as a shunt product in cell free extracts of Streptomyces cattleya.

    Science.gov (United States)

    Cobb, Steven L; Deng, Hai; Hamilton, John T G; McGlinchey, Ryan P; O'Hagan, David; Schaffrath, Christoph

    2005-10-01

    5'-Fluoro-5'-deoxyinosine (5'-FDI) is identified as an adventitious side product that accumulates in cell free incubations of SAM and fluoride ion in Streptomyces cattleya. 5'-FDI was identified by a combination of isotopic labelling studies and co-synthesis studies as well as enzymatic degradation. Although it is an efficiently generated end product of the cell free incubations, 5'-FDI is not a biosynthetic intermediate and it does not accumulate as a fluorometabolite with fluoroacetate and 4-fluorothreonine in whole cell incubations of S. cattleya. Clearly the purine deaminase which converts 5'-fluoro-5'-deoxyadenosine (5'-FDA) to 5'-FDI in the cell free extract does not come into contact with 5'-FDA in whole cells, suggesting some level of compartmentalisation in cells of S. cattleya. The biotransformation of 5'-FDI from fluoride ion extends the range of organofluorine products, beyond biosynthetic intermediates, that can be generated by this system, for applications such as enzymatic labelling with fluorine-18 for positron emission tomography applications.

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Directory of Open Access Journals (Sweden)

    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.

  7. The identification of (3R,4S)-5-fluoro-5-deoxy-D-ribulose-1-phosphate as an intermediate in fluorometabolite biosynthesis in Streptomyces cattleya.

    Science.gov (United States)

    Onega, Mayca; McGlinchey, Ryan P; Deng, Hai; Hamilton, John T G; O'Hagan, David

    2007-10-01

    (3R,4S)-5-Fluoro-5-deoxy-D-ribulose-1-phosphate (5-FDRulP) has been identified as the third fluorinated intermediate on the biosynthetic pathway to fluoroacetate and 4-fluorothreonine in Streptomyces cattleya. 5-FDRulP is generated after formation of 5'-fluoro-5'-deoxyadenosine (5'-FDA) and then phosphorolysis of 5'-FDA to 5-fluoro-5-deoxy-D-ribose-1-phosphate (5-FDRP) by the action of a purine nucleoside phosphorylase. An isomerase mediates the conversion of 5-FDRP to 5-FDRulP. The identity of the (3R,4S) diastereoisomer of 5-FDRulP was established by comparative (19)F{(1)H} NMR studies whereby 5-FDRulP that accumulated in a cell free extract of S. cattleya, was treated with a phytase to generate the non-phosphorylated sugar, 5-fluoro-5-deoxy-D-ribulose (5-FDRul). This S. cattleya product was compared to the product of an in-vitro biotransformation where separately 5-fluoro-5-deoxy-D-ribose and 5-fluoro-5-deoxy-D-xylose were converted to 5-fluoro-5-deoxy-D-ribulose and 5-fluoro-5-deoxy-D-xylulose respectively by the action of glucose isomerase. It was demonstrated that 5-fluoro-5-deoxy-D-ribose gave the identical diastereoisomer to that observed from 5-FDRulP.

  8. 6-Ethyl-5-fluoro-2-methoxypyrimidin-4(3H-one

    Directory of Open Access Journals (Sweden)

    Yu-Yuan Ye

    2009-10-01

    Full Text Available In the title compound, C7H9FN2O2, the methoxy and ethyl groups form dihedral angles of 1.4 (2 and 73.5 (3°, respectively, with the mean plane of the pyrimidine ring. In the crystal structure, two molecules are linked by a pair of N—H...O hydrogen bonds, forming a centrosymmetric dimer.

  9. Radiosynthesis and preliminary PET evaluation of (18)F-labeled 2-(1-(3-fluorophenyl)-2-oxo-5-(pyrimidin-2-yl)-1,2-dihydropyridin-3-yl)benzonitrile for imaging AMPA receptors.

    Science.gov (United States)

    Yuan, Gengyang; Jones, Graham B; Vasdev, Neil; Liang, Steven H

    2016-10-01

    To prompt the development of (18)F-labeled positron emission tomography (PET) tracers for the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor, we have prepared (18)F-labeled 2-(1-(3-fluorophenyl)-2-oxo-5-(pyrimidin-2-yl)-1,2-dihydropyridin-3-yl)benzonitrile ([(18)F]8). The radiosynthesis was achieved by a one-pot two-step method that utilized a spirocyclic hypervalent iodine(III) mediated radiofluorination to prepare the (18)F-labeled 1-bromo-3-fluorobenzene ([(18)F]15) intermediate with K(18)F. A subsequent copper(I) iodide mediated coupling reaction was carried out with 2-(2-oxo-5-(pyrimidin-2-yl)-1,2-dihydropyridin-3-yl)benzonitrile (10) to [(18)F]8 in 10±2% uncorrected radiochemical yield relative to starting (18)F-fluoride with >99% radiochemical purity and 29.6±7.4Gbq/μmol specific activity at the time of injection. PET imaging studies with the title radiotracer in normal mice demonstrated good brain uptake (peak standardized uptake value (SUV)=2.3±0.1) and warrants further in vivo validation.

  10. 5-fluoro-D,L-tryptophan as a dual NMR and fluorescent probe of α-synuclein.

    Science.gov (United States)

    Pfefferkorn, Candace M; Lee, Jennifer C

    2012-01-01

    Analysis of conventional proton nuclear magnetic resonance (NMR) experiments on intrinsically disordered proteins (IDPs) is challenging because of the highly flexible and multiple rapidly exchanging conformations typifying this class of proteins. One method to circumvent some of these difficulties is to incorporate nonnative fluorine ((19)F) nuclei at specific sites within the polypeptide. (19)F NMR is particularly suitable for characterization of unfolded structures because (19)F chemical shifts are highly sensitive to local environments and conformations. Furthermore, the incorporation of fluorine analogs of fluorescent amino acids such as 5-fluoro-D: ,L: -tryptophan (5FW) allows for complementary studies of protein microenvironment via fluorescence spectroscopy. Herein, we describe methods to produce, purify, characterize, and perform steady-state fluorescence and 1D NMR experiments on 5FW analogs of the IDP α-synuclein.

  11. [{sup 18}F]D.P.A.-714: a novel fluorine-18-labelled pyrazolo[1,5-a]pyrimidine acetamide for imaging the peripheral benzodiazepine receptors with PET - radiosynthesis on a zymate-xp robotic system

    Energy Technology Data Exchange (ETDEWEB)

    Dolle, F.; Damont, A.; Hinnen, F.; Kuhnast, B.; Chauveau, F.; Van camp, N.; Hantraye, P.; Tavitian, B. [Servvice Hospitalier Frederic Joliot, I2BM/DSV, 91 - Orsay (France); James, M.; Creelman, A.; Fulton, R.; Kassiou, M. [Sydney Univ., Brain and Mind Research Institute, NSW (Australia); Vercouillie, J.; Guilloteau, D. [Universite Francois Rabelais de Tours, 37 (France); Vercouillie, J.; Guilloteau, D. [Centre Hospitalier Regional Universitaire, 37 - Tours (France); Selleri, S.; Kassiou, M. [Sydney Univ., Discipline of Medical Radiations, Sciences and School of Chemistry, NSW (Australia)

    2008-02-15

    {sup 11}C D.P.A.-713 (N,N-diethyl-2-[2-(4-[{sup 11}C]methoxy-phenyl)-5,7-dimethyl-pyrazolo [1,5-a]pyrimidin-3-yl]acetamide) is a recently developed carbon-11-labelled (half life: 20.4 min)pyrazolo[1,5-a]pyrimidine acetamide for the in vivo imaging of the peripheral benzodiazepine receptors (P.B.R. or translocator protein (18 kDa, T.S.P.O.)). Preliminary results obtained in a rodent-model demonstrates that {sup 11}C D.P.A.-713 showed a high potential to in vivo image neuro-inflammation and additionally, this radioligand allowed a higher contrast between the lesioned area and the corresponding area in the intact contralateral hemisphere when compared to the radioligand of reference. D.P.A-714 (N,N-diethyl-2-[2-[4-(2-fluoro-ethoxy)phenyl] -5,7-dimethyl-pyrazolo[1,5-a]pyrimidin-3-yl]acetamide), a chemically closely related derivative of D.P.A.-713, had been designed with a fluorine atom in its structure, allowing ultimate labelling with fluorine-18, a longer-lived positron-emitter (half life:109.8 min) and today one of the most attractive PET isotopes for radiopharmaceutical chemistry. D.P.A.-714 as well as its corresponding tosylated derivative have been re-synthesized in 2 chemicals steps from D.P.A.-713. D.P.A.-714 has then been labelled at its aromatic fluoro-ethoxy group from the corresponding tosyl-derivative using the K{sup 18}FF-kryptofix{sub 222} (in CH{sub 3}CN (3 mL) at 85 degrees C for 5 min or D.M.S.O. (600 {mu}L) at 130 degrees C for 5 min). {sup 18}FD.P.A.-714 was then purified using semi preparative X terra reverse phase H.P.L.C., adequately formulated for i.v. injection and was found to be > 95% chemically and radiochemically pure. The total synthesis time was less than 90 min and the specific radioactivities at the end of the radiosynthesis ranged from 1 to 3 Ci/micro-mole. (N.C.)

  12. CONVERSION OF LIPOSOMAL 5-FLUORO-2'-DEOXYURIDINE AND ITS DIPALMITOYL DERIVATIVE TO BILE-ACID CONJUGATES OF ALPHA-FLUORO-BETA-ALANINE AND THEIR EXCRETION INTO RAT BILE

    NARCIS (Netherlands)

    WAALKES, MV; KUIPERS, F; HAVINGA, R; SCHERPHOF, GL

    1993-01-01

    We studied the hepatic processing and biliary excretion of metabolites of the radiolabeled cytostatic agent 5-fluoro,-2'-deoxy[6-H-3]uridine (FUdR) and its lipophilic derivative FUdR-dipalmitate incorporated in liposomes. After intracardial injection in rats, free FUdR was cleared from the circulati

  13. Human Hepatocyte Metabolism of Novel Synthetic Cannabinoids MN-18 and Its 5-Fluoro Analog 5F-MN-18.

    Science.gov (United States)

    Diao, Xingxing; Carlier, Jeremy; Zhu, Mingshe; Huestis, Marilyn A

    2017-08-18

    In 2014, 2 novel synthetic cannabinoids, MN-18 and its 5-fluoro analog, 5F-MN-18, were first identified in an ongoing survey of novel psychoactive substances in Japan. In vitro pharmacological assays revealed that MN-18 and 5F-MN-18 displayed high binding affinities to human CB1 and CB2 receptors, with Ki being 1.65-3.86 nmol/L. MN-18 and 5F-MN-18 were scheduled in Japan and some other countries in 2014. Despite increasing prevalence, no human metabolism data are currently available, making it challenging for forensic laboratories to confirm intake of MN-18 or 5F-MN-18. We incubated 10 μ mol/L of MN-18 and 5F-MN-18 in human hepatocytes for 3 h and analyzed the samples on a TripleTOF 5600(+) high-resolution mass spectrometer to identify appropriate marker metabolites. Data were acquired via full scan and information-dependent acquisition-triggered product ion scans with mass defect filter. In total, 13 MN-18 metabolites were detected, with the top 3 abundant metabolites being 1-pentyl-1H-indazole-3-carboxylic acid, pentyl-carbonylated MN-18, and naphthalene-hydroxylated MN-18. For 5F-MN-18, 20 metabolites were observed, with the top 3 abundant metabolites being 5`-OH-MN-18, MN-18 pentanoic acid, and 1-(5-fluoropentyl)-1H-indazole-3-carboxylic acid. We have characterized MN-18 and 5F-MN-18 metabolism with human hepatocytes and high-resolution mass spectrometry, and we recommend characteristic major metabolites for clinical and forensic laboratories to identify MN-18 and 5F-MN-18 intake and link observed adverse events to these novel synthetic cannabinoids. © 2017 American Association for Clinical Chemistry.

  14. Neo-adjuvant chemoradiotherapy by 5-fluoro-uracil and oxaliplatine for the locally evolved rectum cancer: study of the toxicity and the histological response; Chimioradiotherapie neoadjuvante par 5-fluoro-uracile et oxaliplatine pour les cancers du rectum localement evolues: etude de la toxicite et de la reponse histologique

    Energy Technology Data Exchange (ETDEWEB)

    Le Scodan, R.; Miranda, O.; Henni, M.; Durdux, C.; Housset, M. [HEGP, Dept. de Radiotherapie, 75 - Paris (France); Landi, B. [HEGP, Dept. de Gastroenterologie, 75 - Paris (France); Berger, A. [HEGP, Dept. Chirurgie Viscerale, 75 - Paris (France); Dousset, B. [Hopital Cochin, Dept. de Chirurgie Viscerale, 75 - Paris (France); Brezault, C. [Hopital Cochin, Dept. Gastroenterologie, 75 - Paris (France); Cote, J.F. [HEGP, Dept. d' anatomopathologie, 75 - Paris (France)

    2006-11-15

    The neo-adjuvant chemoradiotherapy by 5-fluoro-uracil and oxaliplatine, for the locally evolved rectum cancers, has a certain efficiency in term of histological response with an acceptable acute toxicity. The study of prediction factors to the response to chemoradiotherapy is in progress. (N.C.)

  15. Pyrimidine-pyridine ring interconversion

    NARCIS (Netherlands)

    Plas, van der H.C.

    2003-01-01

    This chapter discusses the pyrimidine-to-pyridine ring transformation and pyridine-to-pyrimidine ring transformation. In nucleophile-induced pyrimidine-to-pyridine rearrangements, two types of reactions can be distinguished depending on the structure of the nucleophile: (1) reactions in which the ni

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

  17. Purine and pyrimidine metabolism.

    Science.gov (United States)

    Zöllner, N

    1982-09-01

    The pathways of purine biosynthesis and degradation have been elucidated during the last 30 years; the regulation of the mechanisms involved is not yet fully understood, particularly with respect to quantitative aspects. Research into inborn errors of purine metabolism has provided valuable insights into purine synthesis and salvage pathways. Nutrition experiments using purine-free formula diets and supplements with defined purine sources permit precise descriptions of the influence of various dietary purines on uric acid formation. Supplements of dietary purines produce dose-proportional increases in plasma uric acid concentrations, uric acid pool size and renal uric acid excretion. The magnitude of these increases depends on the type of purine compound administered, which may limit the value of food tables for human dietetics. Purine content of food must be related not only to weight but also to energy and to protein, particularly if new foodstuffs or a vegetarian diet are ingested. Dietary purines appear to influence the biosynthesis of pyrimidines. In contrast to dietary purines, pyrimidines in the diet, if administered as nucleosides or nucleotides, are utilized in animals for the synthesis of nucleic acids. Much further work is necessary for a better understanding of the inter-relationships of purine and pyrimidine metabolism.

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

    Institute of Scientific and Technical Information of China (English)

    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.

  19. A Search for Interstellar Pyrimidine

    CERN Document Server

    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.

  20. Pentylindole/Pentylindazole Synthetic Cannabinoids and Their 5-Fluoro Analogs Produce Different Primary Metabolites: Metabolite Profiling for AB-PINACA and 5F-AB-PINACA.

    Science.gov (United States)

    Wohlfarth, Ariane; Castaneto, Marisol S; Zhu, Mingshe; Pang, Shaokun; Scheidweiler, Karl B; Kronstrand, Robert; Huestis, Marilyn A

    2015-05-01

    Whereas non-fluoropentylindole/indazole synthetic cannabinoids appear to be metabolized preferably at the pentyl chain though without clear preference for one specific position, their 5-fluoro analogs' major metabolites usually are 5-hydroxypentyl and pentanoic acid metabolites. We determined metabolic stability and metabolites of N-(1-amino-3-methyl-1-oxobutan-2-yl)-1-pentyl-1H-indazole-3-carboxamide (AB-PINACA) and 5-fluoro-AB-PINACA (5F-AB-PINACA), two new synthetic cannabinoids, and investigated if results were similar. In silico prediction was performed with MetaSite (Molecular Discovery). For metabolic stability, 1 μmol/L of each compound was incubated with human liver microsomes for up to 1 h, and for metabolite profiling, 10 μmol/L was incubated with pooled human hepatocytes for up to 3 h. Also, authentic urine specimens from AB-PINACA cases were hydrolyzed and extracted. All samples were analyzed by liquid chromatography high-resolution mass spectrometry on a TripleTOF 5600+ (AB SCIEX) with gradient elution (0.1% formic acid in water and acetonitrile). High-resolution full-scan mass spectrometry (MS) and information-dependent acquisition MS/MS data were analyzed with MetabolitePilot (AB SCIEX) using different data processing algorithms. Both drugs had intermediate clearance. We identified 23 AB-PINACA metabolites, generated by carboxamide hydrolysis, hydroxylation, ketone formation, carboxylation, epoxide formation with subsequent hydrolysis, or reaction combinations. We identified 18 5F-AB-PINACA metabolites, generated by the same biotransformations and oxidative defluorination producing 5-hydroxypentyl and pentanoic acid metabolites shared with AB-PINACA. Authentic urine specimens documented presence of these metabolites. AB-PINACA and 5F-AB-PINACA produced suggested metabolite patterns. AB-PINACA was predominantly hydrolyzed to AB-PINACA carboxylic acid, carbonyl-AB-PINACA, and hydroxypentyl AB-PINACA, likely in 4-position. The most intense 5F

  1. The cytostatic activity of NUC-3073, a phosphoramidate prodrug of 5-fluoro-2'-deoxyuridine, is independent of activation by thymidine kinase and insensitive to degradation by phosphorolytic enzymes.

    Science.gov (United States)

    Vande Voorde, Johan; Liekens, Sandra; McGuigan, Christopher; Murziani, Paola G S; Slusarczyk, Magdalena; Balzarini, Jan

    2011-09-01

    A novel phosphoramidate nucleotide prodrug of the anticancer nucleoside analogue 5-fluoro-2'-deoxyuridine (5-FdUrd) was synthesized and evaluated for its cytostatic activity. Whereas 5-FdUrd substantially lost its cytostatic potential in thymidine kinase (TK)-deficient murine leukaemia L1210 and human lymphocyte CEM cell cultures, NUC-3073 markedly kept its antiproliferative activity in TK-deficient tumour cells, and thus is largely independent of intracellular TK activity to exert its cytostatic action. NUC-3073 was found to inhibit thymidylate synthase (TS) in the TK-deficient and wild-type cell lines at drug concentrations that correlated well with its cytostatic activity in these cells. NUC-3073 does not seem to be susceptible to inactivation by catabolic enzymes such as thymidine phosphorylase (TP) and uridine phosphorylase (UP). These findings are in line with our observations that 5-FdUrd, but not NUC-3073, substantially loses its cytostatic potential in the presence of TP-expressing mycoplasmas in the tumour cell cultures. Therefore, we propose NUC-3073 as a novel 5-FdUrd phosphoramidate prodrug that (i) may circumvent potential resistance mechanisms of tumour cells (e.g. decreased TK activity) and (ii) is not degraded by catabolic enzymes such as TP which is often upregulated in tumour cells or expressed in mycoplasma-infected tumour tissue.

  2. Correlation of thymidylate synthase, thymidine phosphorylase and dihydropyrimidine dehydrogenase with sensitivity of gastrointestinal cancer cells to 5-fluorouracil and 5-fluoro-2'-deoxyuridine

    Institute of Scientific and Technical Information of China (English)

    Tao Ma; Zheng-Gang Zhu; Yu-Bao Ji; Yi Zhang; Ying-Yan Yu; Bing-Ya Liu; Hao-Ran Yin; Yan-Zhen Lin

    2004-01-01

    AIM: To determine the expression levels of three metabolic enzymes of fluoropyrimidines: thymidylate synthase (TS),thymidine phosphorylase (TP) and dihydropyrimidine dehydrogenase (DPD) in seven human gastrointestinal cancer cell lines, and to compare the enzyme levels with the sensitivity to 5-fluorouracil (5-FU) and 5-fluoro-2'-deoxyuridine (FdUrd).METHODS: TS, TP and DPD mRNA levels were assessed by semi-quantitative RT-PCR, TP and DPD protein contents were measured by ELISA. Fifty percent inhibitory concentrations of growth (IC50), representing the sensitivityto drugs, were determined by MTT assay.RESULTS: IC50 values ranged from 1.28 to 12.26 uM for 5-FU, and from 5.02 to 24.21 uM for FdUrd, respectively.Cell lines with lower DPD mRNA and protein levels tended to be more sensitive to 5-FU (P<0.05), but neither TS nor TP correlated with 5-FU IC50 (P>0.05). Only TS mRNA level was sharply related with FdUrd sensitivity (P<0.05), but TP and DPD were not (P>0.05). A correlation was found between mRNA and protein levels of DPD (P<0.05), but not TP (P<0.05).CONCLUSION: DPD and TS enzyme levels may be useful indicators in predicting the antitumor activity of 5-FU or FdUrd, respectively.

  3. Calpain regulates thymidylate synthase-5-fluoro-dUMP complex levels associated with response to 5-fluorouracil in gastric cancer cells.

    Science.gov (United States)

    Nabeya, Yoshihiro; Suzuki, Takao; Furuya, Aki; Koide, Naoki; Ohkoshi, Motohiro; Takiguchi, Masaki; Ochiai, Takenori; Matsubara, Hisahiro; Hiwasa, Takaki

    2011-08-01

    Thymidylate synthase (TS) plays a major role in the response to 5-fluorouracil (5-FU) by binding directly to the 5-FU metabolite, 5-fluoro-dUMP (FdUMP). The change in the TS expression levels after 5-FU administration was examined in parallel to 5-FU responsiveness in six human gastric adenocarcinoma cell lines to elucidate the source of variability of 5-FU sensitivity. MKN-1, SH-10-TC and MKN-74 cells were more resistant to 5-FU than MKN-28, KATO III and MKN-45 cells. Western blotting analysis revealed that the 5-FU sensitivity of these cells did not correlate with the basal TS expression levels but did correlate with rapid detection of the TS-FdUMP complex after exposure to 5-FU. In 5-FU-resistant cells, very low levels of the TS-FdUMP complex early after 5-FU exposure were elevated by pretreatment with calpain inhibitors such as benzyloxycarbonyl-leucyl-leucinal (ZLLH), benzyloxycarbonyl-leucyl-leucyl-leucinal (ZLLLH) and ALLN, but not by other protease inhibitors. In contrast, ONO-3403, which causes calpain activation, stimulated downregulation of the TS-FdUMP complex in 5-FU-sensitive cells. The expression levels of calpastatin, an endogenous calpain inhibitor, were higher in 5-FU-sensitive cells than in 5-FU-resistant cells. ZLLH increased the 5-FU sensitivity of 5-FU-resistant cells, whereas ONO-3403 decreased the sensitivity of 5-FU-sensitive cells. In addition, knockdown of m-calpain by siRNA increased the 5-FU sensitivity in 5-FU-resistant cells, while knockdown of calpastatin reduced the sensitivity in 5-FU-sensitive cells. These results suggest that calpain might reduce the chemosensitivity of human gastric cancer cells to 5-FU possibly by rapid degradation of the TS-FdUMP complex, a finding that is considered to have novel therapeutic implications.

  4. Phosphorylation of thymidylate synthase affects slow-binding inhibition by 5-fluoro-dUMP and N(4)-hydroxy-dCMP.

    Science.gov (United States)

    Ludwiczak, Jan; Maj, Piotr; Wilk, Piotr; Frączyk, Tomasz; Ruman, Tomasz; Kierdaszuk, Borys; Jarmuła, Adam; Rode, Wojciech

    2016-04-01

    Endogenous thymidylate synthases, isolated from tissues or cultured cells of the same specific origin, have been reported to show differing slow-binding inhibition patterns. These were reflected by biphasic or linear dependence of the inactivation rate on time and accompanied by differing inhibition parameters. Considering its importance for chemotherapeutic drug resistance, the possible effect of thymidylate synthase inhibition by post-translational modification was tested, e.g. phosphorylation, by comparing sensitivities to inhibition by two slow-binding inhibitors, 5-fluoro-dUMP and N(4)-hydroxy-dCMP, of two fractions of purified recombinant mouse enzyme preparations, phosphorylated and non-phosphorylated, separated by metal oxide/hydroxide affinity chromatography on Al(OH)3 beads. The modification, found to concern histidine residues and influence kinetic properties by lowering Vmax, altered both the pattern of dependence of the inactivation rate on time from linear to biphasic, as well as slow-binding inhibition parameters, with each inhibitor studied. Being present on only one subunit of at least a great majority of phosphorylated enzyme molecules, it probably introduced dimer asymmetry, causing the altered time dependence of the inactivation rate pattern (biphasic with the phosphorylated enzyme) and resulting in asymmetric binding of each inhibitor studied. The latter is reflected by the ternary complexes, stable under denaturing conditions, formed by only the non-phosphorylated subunit of the phosphorylated enzyme with each of the two inhibitors and N(5,10)-methylenetetrahydrofolate. Inhibition of the phosphorylated enzyme by N(4)-hydroxy-dCMP was found to be strongly dependent on [Mg(2+)], cations demonstrated previously to also influence the activity of endogenous mouse TS isolated from tumour cells.

  5. Pyrimidine as antiinflammatory agent: A review

    Directory of Open Access Journals (Sweden)

    Amir M

    2007-01-01

    Full Text Available Pyrimidine nucleus exhibited remarkable pharmacological activities. Literature indicates that compounds having pyrimidine nucleus have wide range of therapeutic uses that include antiinflammatory, antibacterial, anticancer, antiviral, antiHIV, antimalarial, antihypertensive, sedatives and hypnotics, anticonvulsant and antihistaminic. The present review provides a broad view of the antiinflammatory activity possessed by compounds having a pyrimidine nucleus.

  6. [Retarded excision of pyrimidine dimers in human unstimulated lymphocytes].

    Science.gov (United States)

    Snopov, S A; Roza, L; de Gruijl, F R

    2006-01-01

    Using immuno-labelling of cyclobutane pyrimidine dimers (CPDs) in nuclei of peripheral lymphocytes after their UVC-irradiation and cultivation, we have found that within the first four hours of cultivation the CPD-specific fluorescent signal from cell nuclei increased. Earlier, a similar increase in binding of antibody specific for pyrimidine (6-4) pyrimidone photoproducts to undenatured DNA isolated from UV-irradiated Chinese hamster ovary cells was reported (Mitchell et al., 1986). Our experiments showed that nucleotide excision repair enzyme might induce such of DNA modification in lymphocyte nuclei that increased specific antibody binding to DNA fragments with lesions. We suggest that enzymatic formation of open structures in DNA predominated qualitatively over dual-incision and excision of these fragments, and resulted in the enhanced exposure of the pyrimidine dimers in nuclei to specific antibodies. The results evidence that nucleotid excision repair in unstimualted human lymphocytes being deficient in dual incision and removal of UV-induced DNA lesions appear to be capable of performing chromatin relaxation and pre-incision uncoiling of DNA fragments with lesions.

  7. Polyurethane Foams with Pyrimidine Rings

    Directory of Open Access Journals (Sweden)

    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.

  8. Inhibition of arenavirus by A3, a pyrimidine biosynthesis inhibitor.

    Science.gov (United States)

    Ortiz-Riaño, Emilio; Ngo, Nhi; Devito, Stefanie; Eggink, Dirk; Munger, Joshua; Shaw, Megan L; de la Torre, Juan Carlos; Martínez-Sobrido, Luis

    2014-01-01

    Arenaviruses merit significant interest as important human pathogens, since several of them cause severe hemorrhagic fever disease that is associated with high morbidity and significant mortality. Currently, there are no FDA-licensed arenavirus vaccines available, and current antiarenaviral therapy is limited to an off-labeled use of the nucleoside analog ribavirin, which has limited prophylactic efficacy. The pyrimidine biosynthesis inhibitor A3, which was identified in a high-throughput screen for compounds that blocked influenza virus replication, exhibits a broad-spectrum antiviral activity against negative- and positive-sense RNA viruses, retroviruses, and DNA viruses. In this study, we evaluated the antiviral activity of A3 against representative Old World (lymphocytic choriomeningitis virus) and New World (Junin virus) arenaviruses in rodent, monkey, and human cell lines. We show that A3 is significantly more efficient than ribavirin in controlling arenavirus multiplication and that the A3 inhibitory effect is in part due to its ability to interfere with viral RNA replication and transcription. We document an additive antiarenavirus effect of A3 and ribavirin, supporting the potential combination therapy of ribavirin and pyrimidine biosynthesis inhibitors for the treatment of arenavirus infections.

  9. Synthesis and evaluation of N-(5-fluoro-2-phenoxyphenyl)-N-(2-[(18)F]fluoromethoxy-d(2)-5-methoxybenzyl)acetamide: a deuterium-substituted radioligand for peripheral benzodiazepine receptor.

    Science.gov (United States)

    Zhang, Ming-Rong; Maeda, Jun; Ito, Takehito; Okauchi, Takashi; Ogawa, Masanao; Noguchi, Junko; Suhara, Tetsuya; Halldin, Christer; Suzuki, Kazutoshi

    2005-03-01

    N-(5-Fluoro-2-phenoxyphenyl)-N-(2-[(18)F]fluoromethoxy-d(2)-5-methoxybenzyl)acetamide ([(18)F]2) is a potent ligand (IC(50): 1.71 nM) for peripheral benzodiazepine receptor (PBR). However, in vivo evaluation on rodents and primates showed that this ligand was unstable and rapidly metabolized to [(18)F]F(-) by defluorination of the [(18)F]fluoromethyl moiety. In this study, we designed a deuterium-substituted analogue, N-(5-fluoro-2-phenoxyphenyl)-N-(2-[(18)F]fluoromethoxy-d(2)-5-methoxybenzyl)acetamide ([(18)F]5) as a radioligand for PBR to reduce the in vivo metabolic rate of the non-deuterated [(18)F]2. The design principle was based on the hypothesis that the deuterium substitution may reduce the rate of defluorination initiated by cleavage of the C-H bond without altering the binding affinity for PBR. The non-radioactive 5 was prepared by reacting diiodomethane-d(2) (CD(2)I(2), 6) with a phenol precursor 7, followed by treatment with tetrabutylammonium fluoride. The ligand [(18)F]5 was synthesized by the alkylation of 7 with [(18)F]fluoromethyl iodide-d(2) ([(18)F]FCD(2)I, [(18)F]9). Compound 5 displayed a similar in vitro affinity to PBR (IC(50): 1.90 nM) with 2. In vivo evaluation demonstrated that [(18)F]5 was metabolized by defluorination to [(18)F]F(-) as a main radioactive component, but its metabolic rate was slower than that of [(18)F]2 in the brain of mice. The deuterium substitution decreased the radioactivity level of [(18)F]5 in the bone of mouse, augmented by the percentage of specific binding to PBR in the rat brain determined by ex vivo autoradiography. However, the PET image of [(18)F]5 for monkey brain showed high radioactivity in the brain and skull, suggesting a possible species difference between rodents and primates.

  10. Measurement of small scalar and dipolar couplings in purine and pyrimidine bases.

    Science.gov (United States)

    Zídek, L; Wu, H; Feigon, J; Sklenár, V

    2001-10-01

    A suite of spin-state-selective excitation (S3E) NMR experiments for the measurements of small one-bond (13C-13C, 15N-13C) and two-bond (1H-13C, 1H-15N) coupling constants in 13C,15N labeled purine and pyrimidine bases is presented. The incorporation of band-selective shaped pulses, elimination of the cross talk between alpha and beta sub-spectra, and accuracy and precision of the proposed approach are discussed. Merits of using S3E rather than alpha/beta-half-filter are demonstrated using results obtained on isotopically labeled DNA oligonucleotides.

  11. Genetic factors influencing pyrimidine-antagonist chemotherapy

    NARCIS (Netherlands)

    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

  12. Biological consequences of cyclobutane pyrimidine dimers

    NARCIS (Netherlands)

    Vink, A.A.; Roza, L.

    2001-01-01

    In the skin many molecules may absorb ultraviolet (UV) radiation upon exposure. In particular, cellular DNA strongly absorbs shorter wavelength solar UV radiation, resulting in various types of DNA damage. Among the DNA photoproducts produced the cyclobutane pyrimidine dimers (CPDs) are predominant.

  13. Enzymology of Pyrimidine Metabolism and Neurodegeneration.

    Science.gov (United States)

    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.

  14. Prebiotic syntheses of purines and pyrimidines.

    Science.gov (United States)

    Basile, B; Lazcano, A; Oró, J

    1984-01-01

    The work done in many laboratories during the last two decades has confirmed that hydrogen cyanide and cyanoacetylene are the two major precursors for the prebiotic synthesis of purines and pyrimidines, respectively. Although several different pathways for the synthesis of purines have been described, they are all variations of the initial mechanism proposed by Oró and Kimball, where hydrogen cyanide leads first to the formation of a 4,5-di-substituted imidazole derivative, and then to the closing of the purine ring with a C1 compound. A number of experiments have shown that purines and pyrimidines can also be obtained from methane, ammonia (nitrogen), and water mixtures, provided an activating source of energy (radiation, electric discharges, etc.) is available. However, in this case the yields are lower by about two orders of magnitude because of the intermediate formation of hydrogen cyanide and cyanoacetylene. The latter two compounds have been found in interstellar space, Titan and other bodies of the solar system. They were probably present in the primordial parent bodies from the solar nebula in concentrations of 10(-2) to 10(-3) M as inferred from recent calculations by Miller and coworkers obtained for the Murchison meteorite. These concentrations should have been sufficient to generate relatively large amounts of purine and pyrimidine bases on the primitive Earth.

  15. A previously undescribed pathway for pyrimidine catabolism.

    Science.gov (United States)

    Loh, Kevin D; Gyaneshwar, Prasad; Markenscoff Papadimitriou, Eirene; Fong, Rebecca; Kim, Kwang-Seo; Parales, Rebecca; Zhou, Zhongrui; Inwood, William; Kustu, Sydney

    2006-03-28

    The b1012 operon of Escherichia coli K-12, which is composed of seven unidentified ORFs, is one of the most highly expressed operons under control of nitrogen regulatory protein C. Examination of strains with lesions in this operon on Biolog Phenotype MicroArray (PM3) plates and subsequent growth tests indicated that they failed to use uridine or uracil as the sole nitrogen source and that the parental strain could use them at room temperature but not at 37 degrees C. A strain carrying an ntrB(Con) mutation, which elevates transcription of genes under nitrogen regulatory protein C control, could also grow on thymidine as the sole nitrogen source, whereas strains with lesions in the b1012 operon could not. Growth-yield experiments indicated that both nitrogens of uridine and thymidine were available. Studies with [(14)C]uridine indicated that a three-carbon waste product from the pyrimidine ring was excreted. After trimethylsilylation and gas chromatography, the waste product was identified by mass spectrometry as 3-hydroxypropionic acid. In agreement with this finding, 2-methyl-3-hydroxypropionic acid was released from thymidine. Both the number of available nitrogens and the waste products distinguished the pathway encoded by the b1012 operon from pyrimidine catabolic pathways described previously. We propose that the genes of this operon be named rutA-G for pyrimidine utilization. The product of the divergently transcribed gene, b1013, is a tetracycline repressor family regulator that controls transcription of the b1012 operon negatively.

  16. Development of a new radioligand, N-(5-fluoro-2-phenoxyphenyl)-N-(2-[18F]fluoroethyl-5-methoxybenzyl)acetamide, for pet imaging of peripheral benzodiazepine receptor in primate brain.

    Science.gov (United States)

    Zhang, Ming-Rong; Maeda, Jun; Ogawa, Masanao; Noguchi, Junko; Ito, Takehito; Yoshida, Yuichiro; Okauchi, Takashi; Obayashi, Shigeru; Suhara, Tetsuya; Suzuki, Kazutoshi

    2004-04-22

    To develop a positron emission tomography (PET) ligand for imaging the 'peripheral benzodiazepine receptor' (PBR) in brain and elucidating the relationship between PBR and brain diseases, four analogues (4-7) of N-(2,5-dimethoxybenzyl)-N-(5-fluoro-2-phenoxyphenyl)acetamide (2) were synthesized and evaluated as ligands for PBR. Of these compounds, fluoromethyl (4) and fluoroethyl (5) analogues had similar or higher affinities for PBR than the parent compound 2 (K(i) = 0.16 nM for PBR in rat brain sections). Iodomethyl analogue 6 displayed a moderate affinity, whereas tosyloxyethyl analogue 7 had weak affinity. Radiolabeling was performed for the fluoroalkyl analogues 4 and 5 using fluorine-18 ((18)F, beta(+); 96.7%, T(1/2) = 109.8 min). Ligands [(18)F]4 and [(18)F]5 were respectively synthesized by the alkylation of desmethyl precursor 3 with [(18)F]fluoromethyl iodide ([(18)F]8) and 2-[(18)F]fluoroethyl bromide ([(18)F]9). The distribution patterns of [(18)F]4 and [(18)F]5 in mice were consistent with the known distribution of PBR. However, compared with [(18)F]5, [(18)F]4 displayed a high uptake in the bone of mice. The PET image of [(18)F]4 for monkey brain also showed significant radioactivity in the bone, suggesting that this ligand was unstable for in vivo defluorination and was not a useful PET ligand. Ligand [(18)F]5 displayed a high uptake in monkey brain especially in the occipital cortex, a region with richer PBR than the other regions in the brain. The radioactivity level of [(18)F]5 in monkey brain was 1.5 times higher than that of [(11)C]2, and 6 times higher than that of (R)-(1-(2-chlorophenyl)-N-[(11)C]methyl,N-(1-methylpropyl)isoquinoline ([(11)C]1). Moreover, the in vivo binding of [(18)F]5 was significantly inhibited by PBR-selective 2 or 1, indicating that the binding of [(18)F]5 in the monkey brain was mainly due to PBR. Metabolite analysis revealed that [(18)F]4 was rapidly metabolized by defluorination to [(18)F]F(-) in the plasma and brain of

  17. Neutral pyrimidine C-H donor as anion receptor

    Institute of Scientific and Technical Information of China (English)

    袁迎雪; 吴娜娜; 韩逸飞; 宋相志; 王洪波

    2016-01-01

    Anion receptors including pyrimidine subunit were designed and synthesized and their binding abilities with various anions were investigated by fluorescence and 1H NMR titration experiments. DFT calculations provided some information for anion recognition. It is confirmed that both of two new pyrimidine anion receptors have the selectivity for Cl−.

  18. Pyrimidine biosynthetic pathway of Baccillus subtilis.

    Science.gov (United States)

    Potvin, B W; Kelleher, R J; Gooder, H

    1975-08-01

    Biochemical and genetic data were obtained from a series of 51 Pyr- strains of Bacillus subtilis. The observed enzymatic deficiencies allowed the mutants to be placed into 12 clases, some of which represent defects in more than one of the six known pyrimidine biosynthetic enzymes. Mapping analysis by transformation has shown that all the Pyr- mutations are located in a single small area of the B. subtilis genome. A correlation of the biochemical defects and the genetic data has been made. Those mutations conferring similar enzymatic deficiencies were found to be contiguous on the B. subtilis map. Regulatory aspects of the pyrimidine pathway have also been investigated and are compared to previously reported results from other organisms. Evidence is presented which bears upon the possible physical association of the first three enzymes and the association of at least some of the enzymes of this pathway with particulate elements of the cell. A model for the organization of the enzymes is presented with dihydroorotate dehydrogenase as the central enzyme in a proposed aggregate.

  19. Fluorinase mediated C-(18)F bond formation, an enzymatic tool for PET labelling.

    Science.gov (United States)

    Deng, Hai; Cobb, Steven L; Gee, Antony D; Lockhart, Andrew; Martarello, Laurent; McGlinchey, Ryan P; O'Hagan, David; Onega, Mayca

    2006-02-14

    The fluorinase enzyme from S. cattleya is applied as a catalyst for the efficient incorporation of [18F]-fluoride into [18F]-5'-fluoro-5'-deoxyadenosine, [18F]-5'-fluoro-5'-deoxyinosine and [18F]-5-fluoro-5-deoxyribose for positron emission tomography (PET) applications.

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

    Institute of Scientific and Technical Information of China (English)

    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.

  1. Synthesis of Polyfunctionally Substituted Fused Pyrimidine Derivatives as Antimicrobial Agents

    Institute of Scientific and Technical Information of China (English)

    EISSA, Abd EI-Monem Mohamed Farag

    2008-01-01

    A variety of pyrimidine derivatives 2--4 and annulated pyrimidine derivatives 5-17 have been synthesized via a sequence of heterocyclization reaction of readily available 6-naphthyl-4-oxo-2-thioxo-1,2,3,4-tetrahydroprimi-dine-5-carbonitrile (1) with different acidic and basic reagents. The new compounds were synthesized with the aim of study of their antimicrobial activity. The structures of all synthesized compounds were elucidated by elemental analysis and spectroscopic studies.

  2. Syntheses of halogen derivatives of L-tryptophan, L-tyrosine and L-phenylalanine labeled with hydrogen isotopes.

    Science.gov (United States)

    Pająk, Małgorzata; Pałka, Katarzyna; Winnicka, Elżbieta; Kańska, Marianna

    2016-01-01

    Halogenated, labeled with tritium and doubly with deuterium and tritium, derivatives of L-tryptophan, i.e. 5'-bromo-[2-(3)H]-, 5'-bromo-[2-(2)H/(3)H]-, 5'-fluoro-[2-(3)H]-5'-fluoro-[2-(2)H/(3)H]-, 6'-fluoro-[2-(3)H]-, 6'-fluoro-[2-(2)H/(3)H]-L-tryptophan, as well as, L-tyrosine, i.e. 3'-fluoro-[2-(3)H]-, 3'-fluoro-[2-(2)H/(3)H]-, 3'-chloro-[2-(3)H]-, and 3'-chloro-[2-(2)H/(3)H]-L-tyrosine, and also L-phenylalanine, i.e. 2'-fluoro-[(3S)-(3)H]-, 2'-fluoro-[(3S)-(2)H/(3) H]-, 2'-chloro-[(3S)-(3)H]-, 2'-chloro-[(3S)-(2)H/(3)H]-, 4'-chloro-[(3S)-(3)H]-, and 4'-chloro-[(3S)-(2)H/(3)H]-L-phenylalanine were synthesized using enzymatic methods. Isotopomers of L-tryptophan were synthesized by coupling of halogenated indoles with S-methyl-L-cysteine carried out in deuteriated or tritiated incubation media. Labeled halogenated derivatives of L-tyrosine were obtained by the enzymatically supported exchange between halogenated L-tyrosine and isotopic water. Labeled halogenated isotopologues of L-Phe were synthesized by the enzymatic addition of ammonia to halogenated cinnamic acid. As a source of hydrogen tritiated water (HTO) and heavy water (D2O) with addition of HTO were used.

  3. Low-energy positron scattering by pyrimidine

    Energy Technology Data Exchange (ETDEWEB)

    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.

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

    DEFF Research Database (Denmark)

    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...

  5. Food Labels

    Science.gov (United States)

    ... Surgery? Choosing the Right Sport for You Shyness 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 ...

  6. Uptake and incorporation of pyrimidines in Euglena gracilis.

    Science.gov (United States)

    Wasternack, C H

    1976-08-01

    In photoorganotrophically grown cells of Euglena gracilis the uptake and incorporation degree of 12 different pyrimidines were tested. The rate of uptake of pyrimidines has distinct maxima in the late log phase and in the stationary phase of cell multiplication. The kinetics of uptake are linear in the first 2 h, do not show saturation at various concentrations and increase with the concetrations. No accumulation of the pyrimidines at various concentrations could be observed in the first 2 h of incubation. Membrane inhibitors as uranyl acetate inhibit the uptake of the reference substance alpha-AIB, which is wellknown transported by an active transport mechanism, but have no effect on uptake rate of uracil and cytosine. It could not be observed an energy requirement tested in temperature dependence and with electron transport inhibitors. Uptake of uridine, uracil, barbituric acid and alpha-AIB is inhibited by cycloheximide in a different manner after 5 - 10 min.

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

    Directory of Open Access Journals (Sweden)

    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.

  8. 5-(2-amimo-4-styryl pyrimidine-4-yl-4-methoxybenzofuran-6-ol

    Directory of Open Access Journals (Sweden)

    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.

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

    DEFF Research Database (Denmark)

    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...

  10. Intramolecular inverse electron demand Diels-Alder reactions of pyrimidines.

    NARCIS (Netherlands)

    Frissen, A.E.

    1990-01-01

    This thesis deals with the intramolecular inverse electron demand Diels-Alder reaction of pyrimidines. The main objective of the study was to investigate the synthetic applicability of this reaction and to get more insight in the electronic and steric effects which determine the reactivity of compou

  11. 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

    Directory of Open Access Journals (Sweden)

    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.

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

    Institute of Scientific and Technical Information of China (English)

    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.

  13. Tetraoxane-pyrimidine nitrile hybrids as dual stage antimalarials.

    Science.gov (United States)

    Oliveira, Rudi; Guedes, Rita C; Meireles, Patrícia; Albuquerque, Inês S; Gonçalves, Lídia M; Pires, Elisabete; Bronze, Maria Rosário; Gut, Jiri; Rosenthal, Philip J; Prudêncio, Miguel; Moreira, Rui; O'Neill, Paul M; Lopes, Francisca

    2014-06-12

    The use of artemisinin or other endoperoxides in combination with other drugs is a strategy to prevent development of resistant strains of Plasmodium parasites. Our previous work demonstrated that hybrid compounds, comprising endoperoxides and vinyl sulfones, were capable of high activity profiles comparable to artemisinin and chloroquine while acting through two distinct mechanisms of action: oxidative stress and falcipain inhibition. In this study, we adapted this approach to a novel class of falcipain inhibitors: peptidomimetic pyrimidine nitriles. Pyrimidine tetraoxane hybrids displayed potent nanomolar activity against three strains of Plasmodium falciparum and falcipain-2, combined with low cytotoxicity. In vivo, a decrease in parasitemia and an increase in survival of mice infected with Plasmodium berghei was observed when compared to control. All tested compounds combined good blood stage activity with significant effects on liver stage parasitemia, a most welcome feature for any new class of antimalarial drug.

  14. 5-Benzothiazole substituted pyrimidine derivatives as HCV replication (replicase) inhibitors.

    Science.gov (United States)

    Arasappan, Ashok; Bennett, Frank; Girijavallabhan, Vinay; Huang, Yuhua; Huelgas, Regina; Alvarez, Carmen; Chen, Lei; Gavalas, Stephen; Kim, Seong-Heon; Kosinski, Aneta; Pinto, Patrick; Rizvi, Razia; Rossman, Randall; Shankar, Bandarpalle; Tong, Ling; Velazquez, Francisco; Venkatraman, Srikanth; Verma, Vishal A; Kozlowski, Joseph; Shih, Neng-Yang; Piwinski, John J; MacCoss, Malcolm; Kwong, Cecil D; Clark, Jeremy L; Fowler, Anita T; Geng, Feng; Kezar, Hollis S; Roychowdhury, Abhijit; Reynolds, Robert C; Maddry, Joseph A; Ananthan, Subramaniam; Secrist, John A; Li, Cheng; Chase, Robert; Curry, Stephanie; Huang, Hsueh-Cheng; Tong, Xiao; Njoroge, F George

    2012-05-01

    Based on a previously identified HCV replication (replicase) inhibitor 1, SAR efforts were conducted around the pyrimidine core to improve the potency and pharmacokinetic profile of the inhibitors. A benzothiazole moiety was found to be the optimal substituent at the pyrimidine 5-position. Due to potential reactivity concern, the 4-chloro residue was replaced by a methyl group with some loss in potency and enhanced rat in vivo profile. Extensive investigations at the C-2 position resulted in identification of compound 16 that demonstrated very good replicon potency, selectivity and rodent plasma/target organ concentration. Inhibitor 16 also demonstrated good plasma levels and oral bioavailability in dogs, while monkey exposure was rather low. Chemistry optimization towards a practical route to install the benzothiazole moiety resulted in an efficient direct C-H arylation protocol.

  15. Pyrimidine Nucleobase Radical Reactivity in DNA and RNA.

    Science.gov (United States)

    Greenberg, Marc M

    2016-11-01

    Nucleobase radicals are major products of the reactions between nucleic acids and hydroxyl radical, which is produced via the indirect effect of ionizing radiation. The nucleobase radicals also result from hydration of cation radicals that are produced via the direct effect of ionizing radiation. The role that nucleobase radicals play in strand scission has been investigated indirectly using ionizing radiation to generate them. More recently, the reactivity of nucleobase radicals resulting from formal hydrogen atom or hydroxyl radical addition to pyrimidines has been studied by independently generating the reactive intermediates via UV-photolysis of synthetic precursors. This approach has provided control over where the reactive intermediates are produced within biopolymers and facilitated studying their reactivity. The contributions to our understanding of pyrimidine nucleobase radical reactivity by this approach are summarized.

  16. Pyrimidine nucleobase radical reactivity in DNA and RNA

    Science.gov (United States)

    Greenberg, Marc M.

    2016-11-01

    Nucleobase radicals are major products of the reactions between nucleic acids and hydroxyl radical, which is produced via the indirect effect of ionizing radiation. The nucleobase radicals also result from hydration of cation radicals that are produced via the direct effect of ionizing radiation. The role that nucleobase radicals play in strand scission has been investigated indirectly using ionizing radiation to generate them. More recently, the reactivity of nucleobase radicals resulting from formal hydrogen atom or hydroxyl radical addition to pyrimidines has been studied by independently generating the reactive intermediates via UV-photolysis of synthetic precursors. This approach has provided control over where the reactive intermediates are produced within biopolymers and facilitated studying their reactivity. The contributions to our understanding of pyrimidine nucleobase radical reactivity by this approach are summarized.

  17. Synthesis and biological evaluation of some New pyrimidine derivatives

    Directory of Open Access Journals (Sweden)

    Firyal Weli Askar

    2017-06-01

    Full Text Available New pyrimidine derivatives comprising azo, schiff's bases, chalcones, and chromene ring moieties were prepared.The newly synthesized compounds have been established on the basis of their m.p., TLC, FT-IR, UV-Vis ,¹H-NMR data and element analysis. These compounds were screened for their antimicrobial and in vitro antioxidant properties. The results of this investigation revealed that these compounds are potent antimicrobial and antioxidant agent.

  18. Synthesis and Antibacterial Activity of Chalcones and Pyrimidine-2-ones

    OpenAIRE

    2005-01-01

    Some new chalcones have been prepared by Claisen-schmidt condensation of ketone and different aromatic aldehydes. These chalcones on condensation with urea in presence of acid gave Pyrimidine-2-ones. The synthesized compounds have been characterized by elemental analysis, IR and 1H NMR spectral data. They have been screened for their antibacterial activity against Gram positive bacteria B. subtillis & S. aureus and Gram negative bacteria E. coli & S. typhi.

  19. Nutrition Labeling

    DEFF Research Database (Denmark)

    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...

  20. Nutrition Labeling

    DEFF Research Database (Denmark)

    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...

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

    Directory of Open Access Journals (Sweden)

    Marcel Mirel Popa

    2015-06-01

    Full Text Available The three possible structural isomers of 4-(pyridylpyrimidine 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-pyridylpyrimidine and 4-(4-pyridylpyrimidine 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-pyridylpyrimidine 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-pyridylpyrimidine and 4-(4-pyridylpyrimidine, are also reported.

  2. 2-(4-Bromophenyl-5-fluoro-3-methylsulfinyl-1-benzofuran

    Directory of Open Access Journals (Sweden)

    Hong Dae Choi

    2009-09-01

    Full Text Available In the title compound, C15H10BrFO2S, the O atom and the methyl group of the methylsulfinyl substituent lie on opposite sides of the plane through the benzofuran fragment. The 4-bromophenyl ring is rotated out of the benzofuran plane [dihedral angle = 38.98 (8°], while the structure is stabilized by an intermolecular C—H...O hydrogen bond and a Br...O halogen bond [3.036 (2 Å] and has an intermolecular C–H...π interaction between the 4-bromophenyl H atom and the benzene ring of an adjacent benzofuran molecule, as well as aromatic π–π interactions between the benzene rings of the benzofuran systems [centroid–centroid distance = 3.482 (3 Å].

  3. 2-(4-Chlorophenyl-3-ethylsulfinyl-5-fluoro-1-benzofuran

    Directory of Open Access Journals (Sweden)

    Hong Dae Choi

    2010-04-01

    Full Text Available In the title compound, C16H12ClFO2S, the 4-chlorophenyl ring is rotated out of the benzofuran plane, as indicated by the dihedral angle of 19.79 (8°. The crystal structure exhibits weak intermolecular C—H...O hydrogen bonds and C—H...π interactions.

  4. 3-Cyclopentylsulfonyl-5-fluoro-2-methyl-1-benzofuran

    Directory of Open Access Journals (Sweden)

    Pil Ja Seo

    2011-07-01

    Full Text Available There are two independent molecules, A and B, in the asymmetric unit of the title compound, C14H15FO3S, in each of which the cyclopentyl ring adopts an envelope conformation. The benzofuran units in each molecule are essentially planar, with mean deviations from the least-squares plane defined by the nine constituent ring atoms of 0.009 (2 Å for molecule A and 0.013 (2 Å for molecule B. In the crystal, molecules are linked by weak C—H...O hydrogen bonds. In the cyclopentyl ring of molecule B, one C atom is disordered over two positions with site-occupancy factors of 0.60 (2 and 0.40 (2.

  5. 5-Fluoro-2-methyl-3-(4-methylphenylsulfonyl-1-benzofuran

    Directory of Open Access Journals (Sweden)

    Hong Dae Choi

    2012-02-01

    Full Text Available In the title compound, C16H13FO3S, the 4-methylphenyl ring makes a dihedral angle of 76.04 (4° with the mean plane of the benzofuran fragment. In the crystal, molecules are linked by weak C—H...O hydrogen bonds, and by a slipped π–π interaction between the furan and benzene rings of adjacent molecules [centroid–centroid distance = 3.780 (2 Å, interplanar distance = 3.475 (2 Å and slippage = 1.488 (2 Å].

  6. 2-(4-Bromophenyl-5-fluoro-3-phenylsulfinyl-1-benzofuran

    Directory of Open Access Journals (Sweden)

    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].

  7. Sustainability Labeling

    NARCIS (Netherlands)

    Dam, van Y.K.

    2017-01-01

    Sustainability labeling originated from a need to protect the identity of alternative systems of food production and to increase market transparency. From the 1980s onwards sustainability labeling has changed into a policy instrument replacing direct government regulation of the food market, and a

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

    Indian Academy of Sciences (India)

    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.

  9. Palladium-catalyzed regioselective arylation of imidazo[1,2-a]pyrimidine.

    Science.gov (United States)

    Li, Wenjie; Nelson, Dorian P; Jensen, Mark S; Hoerrner, R Scott; Javadi, Gary J; Cai, Dongwei; Larsen, Robert D

    2003-12-11

    Imidazo[1,2-a]pyrimidine can be arylated at the 3-position with aryl bromides in the presence of base and a catalytic amount of palladium. This provides an efficient one-step synthesis of 3-arylimidazo[1,2-a]pyrimidines from the unsubstituted heterocycle. [reaction: see text

  10. Carbon-Carbon Bond Cleavage Reaction: Synthesis of Multisubstituted Pyrazolo[1,5-a]pyrimidines.

    Science.gov (United States)

    Saikia, Pallabi; Gogoi, Sanjib; Boruah, Romesh C

    2015-07-02

    A new carbon-carbon bond cleavage reaction was developed for the efficient synthesis of multisubstituted pyrazolo[1,5-a]pyrimidines. This base induced reaction of 1,3,5-trisubstituted pentane-1,5-diones and substituted pyrazoles afforded good yields of the pyrazolo[1,5-a]pyrimidines.

  11. Synthesis, Radioiodination and Biodistribution Evaluation of 5-(2-amimo-4-styryl pyrimidine-4-yl-4-methoxybenzofuran-6-ol

    Directory of Open Access Journals (Sweden)

    Atteyat A. Labib

    2013-04-01

    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.

  12. Analysis of substrate specificity and kinetics of cyclic nucleotide phosphodiesterases with N'-methylanthraniloyl-substituted purine and pyrimidine 3',5'-cyclic nucleotides by fluorescence spectrometry.

    Directory of Open Access Journals (Sweden)

    Daniel Reinecke

    Full Text Available As second messengers, the cyclic purine nucleotides adenosine 3',5'-cyclic monophosphate (cAMP and guanosine 3',5'-cyclic monophosphate (cGMP play an essential role in intracellular signaling. Recent data suggest that the cyclic pyrimidine nucleotides cytidine 3',5'-cyclic monophosphate (cCMP and uridine 3',5'-cyclic monophosphate (cUMP also act as second messengers. Hydrolysis by phosphodiesterases (PDEs is the most important degradation mechanism for cAMP and cGMP. Elimination of cUMP and cCMP is not completely understood, though. We have shown that human PDEs hydrolyze not only cAMP and cGMP but also cyclic pyrimidine nucleotides, indicating that these enzymes may be important for termination of cCMP- and cUMP effects as well. However, these findings were acquired using a rather expensive HPLC/mass spectrometry assay, the technical requirements of which are available only to few laboratories. N'-Methylanthraniloyl-(MANT-labeled nucleotides are endogenously fluorescent and suitable tools to study diverse protein/nucleotide interactions. In the present study, we report the synthesis of new MANT-substituted cyclic purine- and pyrimidine nucleotides that are appropriate to analyze substrate specificity and kinetics of PDEs with more moderate technical requirements. MANT-labeled nucleoside 3',5'-cyclic monophosphates (MANT-cNMPs are shown to be substrates of various human PDEs and to undergo a significant change in fluorescence upon cleavage, thus allowing direct, quantitative and continuous determination of hydrolysis via fluorescence detection. As substrates of several PDEs, MANT-cNMPs show similar kinetics to native nucleotides, with some exceptions. Finally, they are shown to be also appropriate tools for PDE inhibitor studies.

  13. Synthesis and characterization of novel Schiff bases containing pyrimidine unit

    Directory of Open Access Journals (Sweden)

    Jumbad H. Tomma

    2014-01-01

    Full Text Available The work involves synthesis of novel Schiff base derivatives containing a pyrimidine unit starting with chalcones. 4-Aminoacetophenone was reacted with 4-nitrobenzaldehyde or 4-chlorobenzaldehyde in basic medium giving chalcones, [I]a and [I]b, respectively, by Claisen-Schemidt reaction. The chalcones [I]a and [I]b were reacted with urea in HCl medium giving oxopyrimidines, [II]a and [II]b. They were also reacted with thiourea in basic medium to give thioxopyrimidines, [III]a and [III]b. The novel mono and bis Schiff bases, [VIII]na, [VIII]nb, [IX]na, [IX]nb, [X]na, [X]nb, [XI]na, and [XI]nb were synthesized by the reaction of pyrimidine derivatives; oxopyrimdines, [II]a and [II]b and thioxopyrimidines, [III]a and [III]b with 4-(4′-n-alkoxybenzoloxybenzaldehyde [VI] and polymethylene-α,ω-bis-4-oxybenzaldehydes [VII]m, respectively, in dry benzene using drops of glacial acetic acid as a catalyst. The synthesized compounds were characterized by melting points, elemental analysis, FTIR, and 1H NMR spectroscopy.

  14. Biotransformation and detectability of the new psychoactive substances N,N-diallyltryptamine (DALT) derivatives 5-fluoro-DALT, 7-methyl-DALT, and 5,6-methylenedioxy-DALT in urine using GC-MS, LC-MS(n), and LC-HR-MS/MS.

    Science.gov (United States)

    Michely, Julian A; Brandt, Simon D; Meyer, Markus R; Maurer, Hans H

    2017-02-01

    Derivatives of N,N-diallyltryptamine (DALT) can be classified as new psychoactive substances. Biotransformation and detectability of 5-fluoro-DALT (5-F-DALT), 7-methyl-DALT (7-Me-DALT), and 5,6-methylenedioxy-DALT (5,6-MD-DALT) are described here. Their metabolites detected in rat urine and pooled human liver microsomes were identified by liquid chromatography (LC)-high resolution (HR)-tandem mass spectrometry (MS/MS). In addition, the human cytochrome-P450 (CYP) isoenzymes involved in the main metabolic steps were identified and detectability tested in urine by the authors' urine screening approaches using GC-MS, LC-MS(n), or LC-HR-MS/MS. Aromatic and aliphatic hydroxylations, N-dealkylation, N-oxidation, and combinations could be proposed for all compounds as main pathways. Carboxylation after initial hydroxylation of the methyl group could also be detected for 7-Me-DALT and O-demethylenation was observed for 5,6-MD-DALT. All phase I metabolites were extensively glucuronidated or sulfated. Initial phase I reactions were catalyzed by CYP1A2, CYP2B6, CYP2C9, CYP2C19, CYP2D6, CYP3A4, and CYP3A5. Rat urine samples were analyzed following two different low-dose administrations. GC-MS was not able to monitor consumption reliably, but all three compounds are predicted to be detectable in cases of overdose. The LC-MS(n) and LC-HR-MS/MS approaches were suitable for detecting an intake of all three compounds mainly via their metabolites. However, after the lowest dose, a reliable monitoring could only be achieved for 5-F-DALT via LC-MS(n) and LC-HR-MS/MS and for 7-Me-DALT via LC-HR-MS/MS. The most abundant targets in both LC-MS screenings were one of two hydroxy-aryl metabolites and both corresponding glucuronides for 5-F-DALT, one N-deallyl hydroxy-aryl, the carboxy, and one dihydroxy-aryl metabolite for 7-Me-DALT, and the demethylenyl metabolite, its oxo metabolite, and glucuronide for 5,6-MD-DALT.

  15. Catabolism of pyrimidines in yeast: a tool to understand degradation of anticancer drugs

    DEFF Research Database (Denmark)

    Andersen, G; Merico, A; Björnberg, O;

    2006-01-01

    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...

  16. Stopping power for electrons in pyrimidine in the energy range 20-3000 eV.

    Science.gov (United States)

    Colmenares, R; Sanz, A G; Fuss, M C; Blanco, F; García, G

    2014-01-01

    In this work, we present new experimental electron energy loss distribution functions for pyrimidine (C4H4N2) measured for the incident energy range 30-2000 eV. Theoretical total and elastic cross sections for electron scattering from pyrimidine were calculated using the screening-corrected additivity rule (IAM-SCAR) method. Based on the mean energy loss observed in the experiment and the theoretical integral inelastic cross section, the stopping power for electrons in pyrimidine is calculated in the energy range 20-3000 eV.

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

    DEFF Research Database (Denmark)

    Andersen, Gorm; Merico, A.; Bjornberg, O.

    2006-01-01

    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...

  18. An Efficient, Clean, and Catalyst-Free Synthesis of Fused Pyrimidines Using Sonochemistry

    Directory of Open Access Journals (Sweden)

    M. Mamaghani

    2014-01-01

    Full Text Available In this report, synthesis of indenopyrido[2,3-d]pyrimidine and pyrimido[4,5-b]quinoline derivatives was investigated via one-pot three-component reaction between 6-amino-2-(alkylthio-pyrimidin-4(3Hone, 1,3-indanedione, or 1,3-cyclohexadione and arylaldehyde under ultrasonic irradiation in ethylene glycol as solvent at 65°C. In these reactions fused pyrimidine derivatives were synthesized with high to excellent yields (82–97% and short reaction times (10–33 min.

  19. An Efficient, Clean, and Catalyst-Free Synthesis of Fused Pyrimidines Using Sonochemistry

    OpenAIRE

    2014-01-01

    In this report, synthesis of indenopyrido[2,3-d]pyrimidine and pyrimido[4,5-b]quinoline derivatives was investigated via one-pot three-component reaction between 6-amino-2-(alkylthio)-pyrimidin-4(3H)one, 1,3-indanedione, or 1,3-cyclohexadione and arylaldehyde under ultrasonic irradiation in ethylene glycol as solvent at 65°C. In these reactions fused pyrimidine derivatives were synthesized with high to excellent yields (82–97%) and short reaction times (10–33 min).

  20. Synthesis and comparing the antibacterial activities of pyrimidine derivatives

    Indian Academy of Sciences (India)

    B ANDREWS; K KOMATHI; S MOHAN

    2017-03-01

    A series of 10 derivatives of 5-(5-amino-1,3,4-thiadiazole-2-yl)-3,4-dihydro-6-methyl-4-phenylpyrimidin-2(1H)-one and 10 derivatives of 3,4-dihydro-5-(5-mercapto-4H-1,2,4-triazol-3-yl)-6-methyl-4-phenyl pyrimidin-2(1H)-one have been synthesized. Among the synthesized derivatives, triazole substitutedcompounds have shown higher antibacterial inhibition when compared to the thiadiazole derivatives. All the structures of the newly synthesized compounds have been characterized by IR, 1H and 13C NMR, GC-MS and CHN analysis. Most of the compounds have shown promising antibacterial activity when compared with the standard drug ciprofloxacin.

  1. New insights on pyrimidine signalling within the arterial vasculature

    DEFF Research Database (Denmark)

    Haanes, Kristian Agmund; Spray, Stine; Syberg, Susanne;

    2016-01-01

    and relaxation in the coronary circulation and to establish whether P2Y receptors have different functions along the mouse coronary vascular tree. We tested stable pyrimidine analogues on isolated coronary arteries from P2Y2 and P2Y6 receptor KO mice in a myograph setup. In larger diameter segments of the left...... descending coronary artery (LAD) (lumen diameter~150μm) P2Y6 is the predominant contractile receptor for both UTP (uridine triphosphate) and UDP (uridine diphosphate) induced contraction. In contrast, P2Y2 receptors mediate endothelial-dependent relaxation. However, in smaller diameter LAD segments (lumen...... diameter~50μm), the situation is opposite, with P2Y2 being the contractile receptor and P2Y6 functioning as a relaxant receptor along with P2Y2. Immunohistochemistry was used to confirm smooth muscle and endothelial localization of the receptors. In vivo measurements of blood pressure in WT mice revealed...

  2. 1,4-Bis(pyrimidin-2-ylsulfanylbutane

    Directory of Open Access Journals (Sweden)

    Muhammad Akbar

    2010-11-01

    Full Text Available The –SCH2CH2CH2CH2S– portion of the title compound, C12H14N2S2, adopts an extended zigzag conformation. The angles at the tetrahedral carbon atoms are marginally increased [113.63 (12° and 111.38 (17° for S—C—C and C—C—C respectively] from the idealized tetrahedral angle. The molecule lies on an inversion center located at the mid-point of the butyl chain. In the crystal, there is a π–π stacking interaction between inversion-related pyrimidine rings with mean interplanar spacing of 3.494 (2 Å.

  3. Bis(pyrimidine-2-carboxylato-κ2N,Ocopper(II

    Directory of Open Access Journals (Sweden)

    Bing-Yu Zhang

    2008-01-01

    Full Text Available The title compound, [Cu(C5H3N2O22], was prepared in a water–ethanol solution containing 2-cyanopyrimidine, malonic acid and copper(II nitrate trihydrate. The CuII ion, located on an inversion center, is chelated by two pyrimidine-2-carboxylate anions in a CuO2N2 square-planar geometry. The uncoordinated carboxylate O atom and pyrimidine N atoms are linked to adjacent pyrimidine rings via weak C—H...O and C—H...N hydrogen bonding. π–π Stacking is observed between nearly parallel pyrimidine rings, the centroid-to-centroid separation being 3.8605 (13 Å.

  4. divalent metal complexes of 4-amino-n-pyrimidin-2-ylbenzene ...

    African Journals Online (AJOL)

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    use of metal complexes as chemotherapeutic drugs has become a vibrant and growing area of ..... through the pyrimidine nitrogen atom [17]. ... binding can take place by the acceptance of a one pair of electron from the donor nitrogen atom.

  5. Absorption and Intermediary Metabolism of Purines and Pyrimidines in Lactating Dairy Cows

    DEFF Research Database (Denmark)

    Nielsen, Charlotte Stentoft; Røjen, Betina Amdisen; Jensen, Søren Krogh

    2015-01-01

    About 20 % of ruminal microbial N in dairy cows derives from purines and pyrimidines; however, their intermediary metabolism and contribution to the overall N metabolism has sparsely been described. In the present study, the postprandial patterns of net portal-drained viscera (PDV) and hepatic...... metabolism were assessed to evaluate purine and pyrimidine N in dairy cows. Blood was sampled simultaneously from four veins with eight hourly samples from four multi-catheterised Holstein cows. Quantification of twenty purines and pyrimidines was performed with HPLC–MS/MS, and net fluxes were estimated...... across the PDV, hepatic tissue and total splanchnic tissue (TSP). Concentration differences between veins of fifteen purine and pyrimidine nucleosides (NS), bases (BS) and degradation products (DP) were different from zero (P≤ 0·05), resulting in the net PDV releases of purine NS (0·33–1·3 mmol...

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

    Institute of Scientific and Technical Information of China (English)

    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.

  7. The pyrimidine operon pyrRPB-carA from Lactococcus lactis

    DEFF Research Database (Denmark)

    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....... The expression of the pyrimidine biosynthetic genes including the pyrRPB-carA operon is subject to control at the transcriptional level, most probably by an attenuator mechanism in which PyrR acts as the regulatory protein....

  8. Synthesis and evaluation of chalcone analogues based pyrimidines as angiotensin converting enzyme inhibitors.

    Science.gov (United States)

    Bukhari, S N A; Butt, A M; Amjad, M W B; Ahmad, W; Shah, V H; Trivedi, A R

    2013-11-01

    Hypertension is a widespread and frequently progressive ailment that imparts a foremost threat for cardiovascular and renal disorders. Mammoth efforts are needed for the synthesis of innovative antihypertensive agents to combat this lethal disease. Chalcones have shown antihypertensive activity through inhibition of Angiotensin Converting Enzyme (ACE). Hence, a series of chalcone analogues is synthesized and used as precursor for the synthesis of novel series of pyrimidines. Precursor chalcones were prepared by reacting aldehydes and ketones in presence of sodium hydroxide followed by synthesis of corresponding pyrimidines by reaction with urea in presence of potassium hydroxide. Both groups were then evaluated for their effects on ACE. The results depicted that pyrimidines were more active than chalcones with methoxy (C5 and P5) substitution showing best results to inhibit ACE. Given that chalcone analogues and pyrimidines show a potential as the angiotensin converting enzyme inhibitors.

  9. Food labels

    DEFF Research Database (Denmark)

    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...

  10. The 3-ureidopropionase of Caenorhabditis elegans, an enzyme involved in pyrimidine degradation.

    Science.gov (United States)

    Janowitz, Tim; Ajonina, Irene; Perbandt, Markus; Woltersdorf, Christian; Hertel, Patrick; Liebau, Eva; Gigengack, Ulrike

    2010-10-01

    Pyrimidines are important metabolites in all cells. Levels of cellular pyrimidines are controlled by multiple mechanisms, with one of these comprising the reductive degradation pathway. In the model invertebrate Caenorhabditis elegans, two of the three enzymes of reductive pyrimidine degradation have previously been characterized. The enzyme catalysing the final step of pyrimidine breakdown, 3-ureidopropionase (β-alanine synthase), had only been identified based on homology. We therefore cloned and functionally expressed the 3-ureidopropionase of C. elegans as hexahistidine fusion protein. The purified recombinant enzyme readily converted the two pyrimidine degradation products: 3-ureidopropionate and 2-methyl-3-ureidopropionate. The enzyme showed a broad pH optimum between pH 7.0 and 8.0. Activity was highest at approximately 40 °C, although the half-life of activity was only 65 s at that temperature. The enzyme showed clear Michaelis-Menten kinetics, with a K(m) of 147 ± 26 μM and a V(max) of 1.1 ± 0.1 U·mg protein(-1). The quaternary structure of the recombinant enzyme was shown to correspond to a dodecamer by 'blue native' gel electrophoresis and gel filtration. The organ specific and subcellular localization of the enzyme was determined using a translational fusion to green fluorescent protein and high expression was observed in striated muscle cells. With the characterization of the 3-ureidopropionase, the reductive pyrimidine degradation pathway in C. elegans has been functionally characterized.

  11. Pyrimidine non-nucleoside analogs: A direct synthesis of a novel class of N-substituted amino and N-sulfonamide derivatives of pyrimidines.

    Science.gov (United States)

    Elgemeie, Galal H; Salah, Ali M; Abbas, Nermeen S; Hussein, Hoda A; Mohamed, Reham A

    2017-03-04

    A convenient method for the regioselective synthesis of pyrimidine non-nucleoside analogs was developed. This study reports a novel and efficient method for the synthesis of a new type of N-substituted amino methylsulfanylpyrimidines and the corresponding pyrazolo[3,4-d]pyrimidines. This series of compounds was designed through the reaction of dimethyl N-cyanodithioiminocarbonate with 2-cyano-N'-(thiophen-2-yl-, furan-2-yl- and pyridin-4-ylmethylene)acetohydrazide and N'-(2-cyanoacetyl)arylsulfonohydrazides. The scope and limitation of the method are demonstrated. The antibacterial and antifungal activities of the synthesized compounds were also evaluated.

  12. Introduction to Pesticide Labels

    Science.gov (United States)

    Pesticide product labels provide critical information about how to safely and legally handle and use pesticide products. Unlike most other types of product labels, pesticide labels are legally enforceable. Learn about pesticide product labels.

  13. Food Label and You

    Medline Plus

    Full Text Available ... Products Food Home Food Ingredients, Packaging & Labeling Labeling & Nutrition The Food Label and You — Video Share Tweet ... FDA has issued final changes to update the Nutrition Facts label for packaged foods. For more information, ...

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

  15. Synthesis of pyrazolo[1,5-a]pyrimidine derivatives and their antifungal activities against phytopathogenic fungi in vitro.

    Science.gov (United States)

    Zhang, Jin; Peng, Ju-Fang; Bai, Yu-Bin; Wang, Ping; Wang, Tao; Gao, Jin-Ming; Zhang, Zun-Ting

    2016-11-01

    5,6-Diarylpyrazolo[1,5-a]pyrimidines (3) and 6,7-diarylpyrazolo[1,5-a]pyrimidines (4) were chemoselectively synthesized by the condensation of isoflavone (1) and 3-aminopyrazole (2). 5,6-Diarylpyrazolo[1,5-a]pyrimidines (3) were obtained via microwave irradiation, and 6,7-diarylpyrazolo[1,5-a]pyrimidines (4) were obtained via conventional heating. In addition, the pyrimidine derivatives 3 and 4 were evaluated against five phytopathogenic fungi (Cytospora sp., Colletotrichum gloeosporioides, Botrytis cinerea, Alternaria solani, and Fusarium solani) using the mycelium growth rate method. Some of them were effective in inhibiting the growth of the five phytopathogenic fungi. For instance, 6,7-diarylpyrazolo[1,5-a]pyrimidines (4j) inhibited the growth of A. solani with an [Formula: see text] value of 17.11 [Formula: see text], and 6,7-diarylpyrazolo[1,5-a]pyrimidines (4h) inhibited the growth of both Cytospora sp. and F. solani with [Formula: see text] values of 27.32 and 21.04 [Formula: see text], respectively. A chemoselective synthesis of 5,6-pyrazolo[1,5-a]pyrimidines 3 derivatives in excellent yields was performed under microwave irradiation and 6,7-pyrazolo[1,5-a]pyrimidines 4 were also prepared using heating method. The antifungal properties of 3 and 4 were tested against Cytospora sp., Colletotrichum gloeosporioides, Botrytis cinerea, Alternaria solani, and Fusarium solani.

  16. On Online Labeling with Polynomially Many Labels

    DEFF Research Database (Denmark)

    Babka, Martin; Bulánek, Jan; Cunat, Vladimír

    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...

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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.

  19. Ultraviolet light-induced cyclobutane pyrimidine dimers in rabbit eyes.

    Science.gov (United States)

    Mallet, Justin D; Rochette, Patrick J

    2011-01-01

    Sunlight exposure of the eye leads to pathologies including photokeratitis, cortical cataracts, pterygium, actinic conjunctivitis and age-related macular degeneration. It is well established that exposure to ultraviolet (UV) radiations leads to DNA damage, mainly cyclobutane pyrimidine dimers (CPDs). CPD formation is the principal factor involved in skin cancer. However, the exact mechanism by which sunlight induces ocular pathologies is not well understood. To shed light on this issue, we quantified the CPD formation onto DNA of rabbit ocular cells following UVB exposure. We found that CPDs were induced only in the structures of the ocular anterior chamber (cornea, iris and lens) and were more concentrated in the corneal epithelium. Residual UVB that pass through the cornea are completely absorbed by the anterior layers of the iris. CPDs were also detected in the central portion of the lens that is not protected by the iris (pupil). By determining the UV-induced DNA damage formation in eyes, we showed that anterior ocular structures are a reliable physical barrier that protects the subjacent structures from the toxic effects of UV. Although the corneal epithelium is the structure where most of the CPDs were detected, no cancer is related to solar exposure.

  20. Fenarimol, a Pyrimidine-Type Fungicide, Inhibits Brassinosteroid Biosynthesis

    Directory of Open Access Journals (Sweden)

    Keimei Oh

    2015-07-01

    Full Text Available The plant steroid hormone brassinosteroids (BRs are important signal mediators that regulate broad aspects of plant growth and development. With the discovery of brassinoazole (Brz, the first specific inhibitor of BR biosynthesis, several triazole-type BR biosynthesis inhibitors have been developed. In this article, we report that fenarimol (FM, a pyrimidine-type fungicide, exhibits potent inhibitory activity against BR biosynthesis. FM induces dwarfism and the open cotyledon phenotype of Arabidopsis seedlings in the dark. The IC50 value for FM to inhibit stem elongation of Arabidopsis seedlings grown in the dark was approximately 1.8 ± 0.2 μM. FM-induced dwarfism of Arabidopsis seedlings could be restored by brassinolide (BL but not by gibberellin (GA. Assessment of the target site of FM in BR biosynthesis by feeding BR biosynthesis intermediates indicated that FM interferes with the side chain hydroxylation of BR biosynthesis from campestanol to teasterone. Determination of the binding affinity of FM to purified recombinant CYP90D1 indicated that FM induced a typical type II binding spectrum with a Kd value of approximately 0.79 μM. Quantitative real-time PCR analysis of the expression level of the BR responsive gene in Arabidopsis seedlings indicated that FM induces the BR deficiency in Arabidopsis.

  1. Potential formation of three pyrimidine bases in interstellar regions

    CERN Document Server

    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 ...

  2. Lead optimization through VLAK protocol: new annelated pyrrolo-pyrimidine derivatives as antitumor agents.

    Science.gov (United States)

    Lauria, Antonino; Patella, Chiara; Abbate, Ilenia; Martorana, Annamaria; Almerico, Anna Maria

    2012-09-01

    The chemometric protocol VLAK was applied to predict improvement of the biological activity of pyrrolo-pyrimidine derivatives as anticancer agents, by using the NCI ACAM Database as depository of antitumor drugs with a known mechanism of action. Among the selected compounds two of these showed a good increase in the antitumor activity. These new pyrrolo-pyrimidine compounds were demonstrated effective against the full panels of NCI DTP tumour human cell lines. The derivative 8-[3-(piperidino)propyl]-4,10-dimethyl-9-phenyl-6-(methylsulfanyl)-3,4-dihydropyrimido[1,2-c]pyrrolo[3,2-e]pyrimidin-2(8H)-one reveled efficacious against the leukemia subpanel, in particular the RPMI cell line resulted the most sensitive (pGI(50) = 6.68). Moreover the derivative 7-(3-Chloropropyl)-9-methyl-5-(methylsulfanyl)-8-phenyl-3H-imidazo[1,2-c]pyrrolo[3,2-e]pyrimidin-2(7H)-one showed a good antitumor activity against the leukemia subpanel with a low cytotoxic activity, above all against the HCT11 human tumour cell line. The VLAK protocol revealed a good method to design new molecules with good antitumor activity, starting from low active compounds. Moreover this protocol focused on the pyrrolo-pyrimidine derivatives as useful starting point for further development to obtain more potent antitumor agents.

  3. Chemical modification of the third strand: differential effects on purine and pyrimidine triple helix formation.

    Science.gov (United States)

    Mills, Martin; Arimondo, Paola B; Lacroix, Laurent; Garestier, Thérèse; Klump, Horst; Mergny, Jean-Louis

    2002-01-08

    DNA triple helices offer exciting perspectives toward oligonucleotide-directed control of gene expression. Oligonucleotide analogues are routinely used with modifications in either the backbone or the bases to form more stable triple-helical structures or to prevent their degradation in cells. In this article, different chemical modifications are tested in a model system, which sets up a competition between the purine and pyrimidine motifs. For most modifications, the DeltaH degrees of purine triplex formation is close to zero, implying a nearly temperature-independent affinity constant. In contrast, the pyrimidine triplex is strongly favored at lower temperatures. The stabilization induced by modifications previously known to be favorable to the pyrimidine motif was quantified. Interestingly, modifications favorable to the GT motif (propynyl-U and dU replacing T) were also discovered. In a system where two third strands compete for triplex formation, replacement of the GA or GT strand by a pyrimidine strand may be observed at neutral pH upon lowering the temperature. This purine-to-pyrimidine triplex conversion depends on the chemical nature of the triplex-forming strands and the stability of the corresponding triplexes.

  4. Synthesis, crystal structure, characterization and antifungal activity of pyrazolo[1,5-a]pyrimidines derivatives

    Science.gov (United States)

    Zhang, Jin; Peng, Ju-Fang; Wang, Tao; Wang, Ping; Zhang, Zun-Ting

    2016-09-01

    Under microwave radiation, isomers 2-(pyrazolo[1,5-a]pyrimidin-5-yl)phenols (3) and 2-(pyrazolo[1,5-a]pyrimidin-7-yl)phenols (4) were simultaneously obtained by the condensation of chromones and 3-aminopyrazoles. These two isomers were fully characterized by IR, 1H NMR, 13C NMR and HRMS. In addition, a representative product 5-chloro-2-(2-methyl-pyrazolo[1,5-a] pyrimidin-5-yl)phenol (3e) was further conformed by the single crystal X-ray diffraction. The antifungal abilities of the obtained products 3 and 4 were evaluated against five phytopathogenic fungi (Cytospora sp., Colletotrichum gloeosporioides, Botrytis cinerea, Alternaria solani and Fusarium solani). The results revealed that 2-(pyrazolo[1,5-a]pyrimidin-5-yl)phenol (3a) and 4-chloro-2-(2-methylpyrazolo[1,5-a]pyrimidin-7-yl)phenol (4e) exhibited good antifungal abilities against Colletotrichum gloeosporioides with the IC50 values of 24.90 and 28.28 μg/mL, respectively.

  5. Divergent prebiotic synthesis of pyrimidine and 8-oxo-purine ribonucleotides

    Science.gov (United States)

    Stairs, Shaun; Nikmal, Arif; Bučar, Dejan-Krešimir; Zheng, Shao-Liang; Szostak, Jack W.; Powner, Matthew W.

    2017-05-01

    Understanding prebiotic nucleotide synthesis is a long standing challenge thought to be essential to elucidating the origins of life on Earth. Recently, remarkable progress has been made, but to date all proposed syntheses account separately for the pyrimidine and purine ribonucleotides; no divergent synthesis from common precursors has been proposed. Moreover, the prebiotic syntheses of pyrimidine and purine nucleotides that have been demonstrated operate under mutually incompatible conditions. Here, we tackle this mutual incompatibility by recognizing that the 8-oxo-purines share an underlying generational parity with the pyrimidine nucleotides. We present a divergent synthesis of pyrimidine and 8-oxo-purine nucleotides starting from a common prebiotic precursor that yields the β-ribo-stereochemistry found in the sugar phosphate backbone of biological nucleic acids. The generational relationship between pyrimidine and 8-oxo-purine nucleotides suggests that 8-oxo-purine ribonucleotides may have played a key role in primordial nucleic acids prior to the emergence of the canonical nucleotides of biology.

  6. Adaptive Reprogramming of De Novo Pyrimidine Synthesis Is a Metabolic Vulnerability in Triple-Negative Breast Cancer.

    Science.gov (United States)

    Brown, Kristin K; Spinelli, Jessica B; Asara, John M; Toker, Alex

    2017-04-01

    Chemotherapy resistance is a major barrier to the treatment of triple-negative breast cancer (TNBC), and strategies to circumvent resistance are required. Using in vitro and in vivo metabolic profiling of TNBC cells, we show that an increase in the abundance of pyrimidine nucleotides occurs in response to chemotherapy exposure. Mechanistically, elevation of pyrimidine nucleotides induced by chemotherapy is dependent on increased activity of the de novo pyrimidine synthesis pathway. Pharmacologic inhibition of de novo pyrimidine synthesis sensitizes TNBC cells to genotoxic chemotherapy agents by exacerbating DNA damage. Moreover, combined treatment with doxorubicin and leflunomide, a clinically approved inhibitor of the de novo pyrimidine synthesis pathway, induces regression of TNBC xenografts. Thus, the increase in pyrimidine nucleotide levels observed following chemotherapy exposure represents a metabolic vulnerability that can be exploited to enhance the efficacy of chemotherapy for the treatment of TNBC.Significance: The prognosis for patients with TNBC with residual disease after chemotherapy is poor. We find that chemotherapy agents induce adaptive reprogramming of de novo pyrimidine synthesis and show that this response can be exploited pharmacologically, using clinically approved inhibitors of de novo pyrimidine synthesis, to sensitize TNBC cells to chemotherapy. Cancer Discov; 7(4); 391-9. ©2017 AACR.See related article by Mathur et al., p. 380This article is highlighted in the In This Issue feature, p. 339.

  7. Substrate specificity of pyrimidine nucleoside phosphorylases of NP-II family probed by X-ray crystallography and molecular modeling

    Science.gov (United States)

    Balaev, V. V.; Lashkov, A. A.; Prokofev, I. I.; Gabdulkhakov, A. G.; Seregina, T. A.; Mironov, A. S.; Betzel, C.; Mikhailov, A. M.

    2016-09-01

    Pyrimidine nucleoside phosphorylases, which are widely used in the biotechnological production of nucleosides, have different substrate specificity for pyrimidine nucleosides. An interesting feature of these enzymes is that the three-dimensional structure of thymidine-specific nucleoside phosphorylase is similar to the structure of nonspecific pyrimidine nucleoside phosphorylase. The three-dimensional structures of thymidine phosphorylase from Salmonella typhimurium and nonspecific pyrimidine nucleoside phosphorylase from Bacillus subtilis in complexes with a sulfate anion were determined for the first time by X-ray crystallography. An analysis of the structural differences between these enzymes demonstrated that Lys108, which is involved in the phosphate binding in pyrimidine nucleoside phosphorylase, corresponds to Met111 in thymidine phosphorylases. This difference results in a decrease in the charge on one of the hydroxyl oxygens of the phosphate anion in thymidine phosphorylase and facilitates the catalysis through SN2 nucleophilic substitution. Based on the results of X-ray crystallography, the virtual screening was performed for identifying a potent inhibitor (anticancer agent) of nonspecific pyrimidine nucleoside phosphorylase, which does not bind to thymidine phosphorylase. The molecular dynamics simulation revealed the stable binding of the discovered compound—2-pyrimidin-2-yl-1H-imidazole-4-carboxylic acid—to the active site of pyrimidine nucleoside phosphorylase.

  8. Pyrimidine pool imbalance induced by BLM helicase deficiency contributes to genetic instability in Bloom syndrome.

    Science.gov (United States)

    Chabosseau, Pauline; Buhagiar-Labarchède, Géraldine; Onclercq-Delic, Rosine; Lambert, Sarah; Debatisse, Michelle; Brison, Olivier; Amor-Guéret, Mounira

    2011-06-28

    Defects in DNA replication are associated with genetic instability and cancer development, as illustrated in Bloom syndrome. Features of this syndrome include a slowdown in replication speed, defective fork reactivation and high rates of sister chromatid exchange, with a general predisposition to cancer. Bloom syndrome is caused by mutations in the BLM gene encoding a RecQ helicase. Here we report that BLM deficiency is associated with a strong cytidine deaminase defect, leading to pyrimidine pool disequilibrium. In BLM-deficient cells, pyrimidine pool normalization leads to reduction of sister chromatid exchange frequency and is sufficient for full restoration of replication fork velocity but not the fork restart defect, thus identifying the part of the Bloom syndrome phenotype because of pyrimidine pool imbalance. This study provides new insights into the molecular basis of control of replication speed and the genetic instability associated with Bloom syndrome. Nucleotide pool disequilibrium could be a general phenomenon in a large spectrum of precancerous and cancer cells.

  9. Thiolated pyrimidine nucleotides may interfere thiol groups concentrated at lipid rafts of HIV-1 infected cells.

    Science.gov (United States)

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

    2014-12-01

    Upon HIV infection, cells become activated and cell surface thiols are present in increased number. Earlier we demonstrated in vitro anti-HIV effect of thiolated pyrimidine nucleotide UD29, which interferes thiol function. To further analyse the redox processes required for HIV-1 entry and infection, toxicity assays were performed using HIV-1 infected monolayer HeLaCD4-LTR/ β-gal cells and suspension H9 T cells treated with several thiolated nucleotide derivatives of UD29. Selective cytotoxicity of thiolated pyrimidines on HIV-1 infected cells were observed. Results indicate that thiolated pyrimidine derivates may interfere with -SH (thiol) groups concentrated in lipid rafts of cell membrane and interacts HIV-1 infected (activated) cells resulting in a selective cytotoxicity of HIV-1 infected cells, and reducing HIV-1 entry.

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

    Science.gov (United States)

    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.

  11. Transport of pyrimidine nucleosides in cells of Escherichia coli K 12.

    Science.gov (United States)

    Mygind, B; Munch-Petersen

    1975-11-15

    1. The transport of pyrimidine mucleosides into cells of Escherichis coli has been investigated in mutant strains which cannot metabolize these nucleosides. Such cells transport and concentrate purimidine mucleosides several hindredfold. 2. The transport is inhibited by energy poisons and by sulfhydryl reagents. 3. Pyrimidine mucleosides compete mutually for transport. Adenosine is also a strong competitor while guanosine and inosine are weak competitors. 4. The rate of pyrimidine mucleoside transport is shown to be under control of the cytR and deoR gene products, which are also known to regulate the synthesis of nucleoside-catabolizing enzymes. The transport system is repressed by growth on glucose, as is the synthesis of the enzymes.

  12. Microwave assisted synthesis and antimicrobial activity of some novel pyrimidine derivatives

    Directory of Open Access Journals (Sweden)

    S. J. VAGHASIA

    2007-02-01

    Full Text Available The synthesis of thiazolo [5,4-d]pyrimidines can be achieved from different 5-thiazolidinones, 2-butyl-1H-imidazole-5-carbaldehyde and thiourea using microwave irradiation within 5 min. The structures of the products were supported by FTIR, PMR and mass spectral data. The in vitro antimicrobial activity of the synthesized thiazolo [5,4-d]pyrimidines 1a-j, having substituents at the 1- and 3-positions, were determined by the cup-plate method against several standard strains chosen to define the spectrum and potency of the new compounds. The antimicrobial activities of the thiazolo [5,4-d]pyrimidines 1a-j are compared with those of known chosen standard drugs, viz. ampicillin, chloramphenicol, ciprofloxacin, norfloxacin and griseofulvin.

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

    Science.gov (United States)

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

    2008-12-07

    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).

  14. Synthesis and Antimicrobial Studies of Pyrimidine Pyrazole Heterocycles

    Directory of Open Access Journals (Sweden)

    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.

  15. Poly[tetrakis(selenocyanato-κNbis(methanol-κOtris(μ-pyrimidine-κ2N:N′dicobalt(II

    Directory of Open Access Journals (Sweden)

    Mario Wriedt

    2010-07-01

    Full Text Available In the title compound, [Co2(NCSe4(C4H4N23(CH3OH2]n, the CoII ion is coordinated by three N-bonded pyrimidine ligands, two N-bonded selenocyanate anions and one O-bonded methanol molecule in an octahedral coordination mode. The asymmetric unit consists of one CoII ion, one pyrimidine ligand, two selenocyanate anions and one methanol molecule in general positions as well as one pyrimidine ligand located around a twofold rotation axis. In the crystal structure, the pyrimidine ligands bridge [Co(CNSe2(CH3OH] units into zigzag-like chains, which are further connected by pyrimidine ligands into layers parallel to (010.

  16. Breakdown of the regulatory control of pyrimidine biosynthesis in human breast cancer cells.

    Science.gov (United States)

    Sigoillot, Frederic D; Sigoillot, Severine M; Guy, Hedeel I

    2004-04-20

    The activity of the de novo pyrimidine biosynthetic pathway in the MCF7 breast cancer cells was 4.4-fold higher than that in normal MCF10A breast cells. Moreover, while pyrimidine biosynthesis in MCF10A was tightly regulated, increasing as the culture matured and subsequently down-regulated in confluency, the biosynthetic rate in MCF7 cells remained elevated and invariant in all growth phases. The flux through the pathway is regulated by carbamoyl phosphate synthetase, a component of the multifunctional protein, CAD. The intracellular CAD concentration was 3.5- to 4-fold higher in MCF7 cells, an observation that explains the high rate of pyrimidine biosynthesis but cannot account for the lack of growth-dependent regulation. In MCF10A cells, up-regulation of the pathway in the exponential growth phase resulted from MAP kinase phosphorylation of CAD Thr456. The pathway was subsequently down-regulated by dephosphorylation of P approximately Thr456 and the phosphorylation of CAD by PKA. In contrast, the CAD P approximately Thr456 was persistently phosphorylated in MCF7 cells, while the PKA site remained unphosphorylated and consequently the activity of the pathway was elevated in all growth phases. In support of this interpretation, inhibition of MAP kinase in MCF7 cells decreased CAD P approximately Thr456, increased PKA phosphorylation and decreased pyrimidine biosynthesis. Conversely, transfection of MCF10A with constructs that elevated MAP kinase activity increased CAD P approximately Thr456 and the pyrimidine biosynthetic rate. The differences in the CAD phosphorylation state responsible for unregulated pyrimidine biosynthesis in MCF7 cells are likely to be a consequence of the elevated MAP kinase activity and the antagonism between MAP kinase- and PKA-mediated phosphorylations.

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

    Science.gov (United States)

    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.

  18. Food Label and You

    Medline Plus

    Full Text Available ... Vaccines, Blood & Biologics Animal & Veterinary Cosmetics Tobacco Products Food Home Food Ingredients, Packaging & Labeling Labeling & Nutrition The Food Label and You — Video Share Tweet Linkedin Pin ...

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

    DEFF Research Database (Denmark)

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

    1999-01-01

    . By combining the two described mutations, with a cdd mutation, we will be able to construct strains in which pyrimidine pools can be manipulated by adding different pyrimidine-sources at variable concentrations to the growth media. Since nucleotides are central metabolites, many physiological parameters may......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...

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

    DEFF Research Database (Denmark)

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

    1998-01-01

    . By combining the two described mutations, with a cdd mutation, we will be able to construct strains in which pyrimidine pools can be manipulated by adding different pyrimidine-sources at variable concentrations to the growth media. Since nucleotides are central metabolites, many physiological parameters may......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...

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

    Science.gov (United States)

    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

  2. Design,Synthesis,and Hypnotic Activity of Pyrazolo[1,5-a]pyrimidine Derivatives

    Institute of Scientific and Technical Information of China (English)

    Song Qing WANG; Lin FANG; Xiu Jie LIU; Kang ZHAO

    2004-01-01

    On the basis of the Zaleplon structure, novel pyrazolo[1,5-a]pyrimidines were designed and prepared for studies on their hypnotic activity.This paper reported the synthesis of twelve new 5-methyl-7-substituted-pyrazolo[1,5-a]pyrimidine-3-carbonitrile derivatives by using simple starting materials such as propane dinitrile and triethyl orthoformate.The structures of the derived target compounds were confirmed by their IR and 1H-NMR spectroscopic data.The preliminary pharmacological evaluations indicated that some compounds showed hypnotic activity, while derivative 1c was the most potent one.

  3. Heteroaryl ethers by oxidative palladium catalysis of pyridotriazol-1-yloxy pyrimidines with arylboronic acids.

    Science.gov (United States)

    Bardhan, Sujata; Wacharasindhu, Sumrit; Wan, Zhao-Kui; Mansour, Tarek S

    2009-06-18

    The oxidative palladium-catalyzed cross-coupling of pyrimidines containing pyridotriazol-1-yloxy (OPt) as either a urea or an amide functional group with arylboronic acids in the presence of Cs(2)CO(3) in DME containing 0.6-1.0% H(2)O is described for the preparation of heteroaryl ethers. The bromo substitution in the case of 3-(5-bromo-pyrimidin-2-yloxy)-3H-[1,2,3]triazolo[4,5-b]pyridine 1 could serve as a handle for further elaborations such as Suzuki coupling for attaching varied aryl groups.

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

    Indian Academy of Sciences (India)

    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.

  5. Deep Label Distribution Learning With Label Ambiguity

    Science.gov (United States)

    Gao, Bin-Bin; Xing, Chao; Xie, Chen-Wei; Wu, Jianxin; Geng, Xin

    2017-06-01

    Convolutional Neural Networks (ConvNets) have achieved excellent recognition performance in various visual recognition tasks. A large labeled training set is one of the most important factors for its success. However, it is difficult to collect sufficient training images with precise labels in some domains such as apparent age estimation, head pose estimation, multi-label classification and semantic segmentation. Fortunately, there is ambiguous information among labels, which makes these tasks different from traditional classification. Based on this observation, we convert the label of each image into a discrete label distribution, and learn the label distribution by minimizing a Kullback-Leibler divergence between the predicted and ground-truth label distributions using deep ConvNets. The proposed DLDL (Deep Label Distribution Learning) method effectively utilizes the label ambiguity in both feature learning and classifier learning, which help prevent the network from over-fitting even when the training set is small. Experimental results show that the proposed approach produces significantly better results than state-of-the-art methods for age estimation and head pose estimation. At the same time, it also improves recognition performance for multi-label classification and semantic segmentation tasks.

  6. The Renaissance of Metal-Pyrimidine Nucleobase Coordination Chemistry.

    Science.gov (United States)

    Lippert, Bernhard; Sanz Miguel, Pablo J

    2016-08-16

    The significance of metal ions for the function and properties of DNA and RNA, long seen primarily under biological aspects and medicinal uses, has recently gained a renewed momentum. This is a consequence of the advent of novel applications in the fields of materials science, biotechnology, and analytical sensor chemistry that relate to the designed incorporation of transition metal ions into nucleic acid base pairs. Ag(+) and Hg(2+) ions, binding to pyrimidine (pym) nucleobases, represent major players in this development. Interestingly, these metal ions were the ones that some 60 years ago started the field! At the same time, the mentioned metal ions had demonstrated a "special relationship" with the pym nucleobases cytosine, thymine, and uracil! Parallel work conducted with oligonucleotides and model nucleobases fostered numerous significant details of these interactions, in particular when X-ray crystallography was involved, correcting earlier views occasionally. Our own activities during the past three to four decades have focused on, among others, the coordination chemistry of transition and main-group metal ions with pym model nucleobases, with an emphasis on Pt(II) and Pd(II). It has always been our goal to deduce, if possible, the potential relevance of our findings for biological processes. It is interesting to put our data, in particular for trans-a2Pt(II) (a = NH3 or amine), into perspective with those of other metal ions, notably Ag(+) and Hg(2+). Irrespective of major differences in kinetics and lability/inertness between d(8) and d(10) metal ions, there is also a lot of similarity in structural aspects as a result of the preferred linear coordination geometry of these species. Moreover, the apparent clustering of metal ions to the pym nucleobases, which is presumably essential for the formation of nanoclusters on oligonucleotide scaffolds, is impressively reflected in model systems, as are reasons for inter-nucleobase cross-links containing more

  7. Incorporation of radio-labelled nucleic acid precursors by Theileria parva in bovine blood and salivary glands of Rhipicephalus appendiculatus ticks

    Energy Technology Data Exchange (ETDEWEB)

    Irvin, A.D.; Boarer, C.D.H.; Kurtti, T.J.; Ocama, J.G.R. (International Lab. for Research on Animal Diseases, Nairobi (Kenya))

    1981-12-01

    The uptake of radio-labelled nucleic acid precursors by blood and tick salivary gland forms of Theileria parva was studied. Piroplasms took up tritiated purines, particularly hypoxanthine, but not pyrimidines. Similar uptake was recorded by T. parva, both in tick saliva and in salivary glands maintained in vitro. Intermediate parasite stages were those most readily labelled in glands; this reflected active nucleic acid synthesis associated with rapid parasite division. Radio-labelling of T. parva in tick salivary glands could be of value in procedures used for concentrating and purifying theilerial sporozoites.

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

    Science.gov (United States)

    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 (<=20 K) leads to the formation of pyrimidine derivatives including the nucleobase uracil and its precursor 4(3H)-pyrimidone. These results were confirmed by quantum chemical calculations. When pyrimidine is mixed with combinations of H2O, NH3, CH3OH, and CH4 ices under similar conditions, uracil and cytosine are formed. In the present work we study the formation of 4(3H)-pyrimidone and uracil from the irradiation of pyrimidine in H2O ice with high-energy UV photons (Lyman , He I, and He II lines) provided by a synchrotron source. The photo-destruction of pyrimidine in these H2O ices as well as the formation yields for 4(3H)-pyrimidone and uracil are compared with our previous results in order to study the photo-stability of pyrimidine and the production efficiency of uracil as a function of the photon energy.

  9. Novel inhibitors of Mycobacterium tuberculosis growth based on modified pyrimidine nucleosides and their analogues

    Science.gov (United States)

    Shmalenyuk, E. R.; Kochetkov, S. N.; Alexandrova, L. A.

    2013-09-01

    The review summarizes data on the synthesis and antituberculosis activity of pyrimidine nucleoside derivatives and their analogues. Enzymes from M. tuberculosis as promising targets for prototypes of new-generation drugs are considered. Nucleosides as inhibitors of drug-resistant M. tuberculosis strains are characterized. The bibliography includes 101 references.

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

    Institute of Scientific and Technical Information of China (English)

    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.

  11. Ring transformations in reactions of pyrimidine and N-alkyl-pyridinium salts with nucleophiles

    NARCIS (Netherlands)

    Oostveen, E.A.

    1977-01-01

    Paper IOn treatment with liquid ammonia at -33°C, the quaternary pyrimidinium salts, i.e. 1-methylpyrimidinium methyl sulfate, 1,2-dimethylpyrimidinium iodide, 1,4,6-trimethyl-pyrimidinium iodide and 1,2,4,6-tetramethylpyrimidinium iodide demethylate yielding pyrimidine. 2-methyl-, 4,6-dimethyl- and

  12. Blockage of the pyrimidine biosynthetic pathway affects riboflavin production in Ashbya gossypii.

    Science.gov (United States)

    Silva, Rui; Aguiar, Tatiana Q; Domingues, Lucília

    2015-01-10

    The Ashbya gossypii riboflavin biosynthetic pathway and its connection with the purine pathway have been well studied. However, the outcome of genetic alterations in the pyrimidine pathway on riboflavin production by A. gossypii had not yet been assessed. Here, we report that the blockage of the de novo pyrimidine biosynthetic pathway in the recently generated A. gossypii Agura3 uridine/uracil auxotrophic strain led to improved riboflavin production on standard agar-solidified complex medium. When extra uridine/uracil was supplied, the production of riboflavin by this auxotroph was repressed. High concentrations of uracil hampered this (and the parent) strain growth, whereas excess uridine favored the A. gossypii Agura3 growth. Considering that the riboflavin and the pyrimidine pathways share the same precursors and that riboflavin overproduction may be triggered by nutritional stress, we suggest that overproduction of riboflavin by the A. gossypii Agura3 may occur as an outcome of a nutritional stress response and/or of an increased availability in precursors for riboflavin biosynthesis, due to their reduced consumption by the pyrimidine pathway.

  13. Quantifying the effects of halogen bonding by haloaromatic donors on the acceptor pyrimidine.

    Science.gov (United States)

    Ellington, Thomas L; Reves, Peyton L; Simms, Briana L; Wilson, Jamey L; Watkins, Davita L; Tschumper, Gregory S; Hammer, Nathan I

    2017-02-28

    The effects of intermolecular interactions by a series of haloaromatic halogen bond donors on the normal modes and chemical shifts of the acceptor pyrimidine are investigated by Raman and NMR spectroscopies and electronic structure computations. Halogen bond interactions with pyrimidine's nitrogen atoms shift normal modes to higher energy and shift 1H and 13C NMR peaks upfield in adjacent nuclei. This perturbation of vibrational normal modes is reminiscent of the effects of hydrogen bonded networks of water, methanol, or silver on pyrimidine. The unexpected observation of vibrational red shifts and downfield 13C NMR shifts in some complexes suggests that other intermolecular forces such as pi-interactions are competing with halogen bonding. Natural bond orbital analyses indicate a wide range of charge transfer from pyrimidine to different haloaromatic donors is possible and computed halogen bond binding energies can be larger than a typical hydrogen bond. These results emphasize the importance in strategic selection of substituents and electron withdrawing groups in developing supramolecular structures based on halogen bonding.

  14. beta-Ureidopropionase deficiency: an inborn error of pyrimidine degradation associated with neurological abnormalities.

    NARCIS (Netherlands)

    Kuilenburg, A.B.P. van; Meinsma, R.; Beke, E.; Assmann, B.; Ribes, A.; Lorente, I.; Busch, R.; Mayatepek, E.; Abeling, N.G.G.M.; Cruchten, A.C. van; Stroomer, A.E.; Lenthe, H. van; Zoetekouw, L.; Kulik, W.; Hoffmann, G.F.; Voit, T.; Wevers, R.A.; Rutsch, F.; Gennip, A.H. van

    2004-01-01

    beta-Ureidopropionase deficiency is an inborn error of the pyrimidine degradation pathway, affecting the cleavage of N-carbamyl-beta-alanine and N-carbamyl-beta-aminoisobutyric acid. In this study, we report the elucidation of the genetic basis underlying a beta-ureidopropionase deficiency in four p

  15. Rapid and efficient synthesis of fused heterocyclic pyrimidines under ultrasonic irradiation.

    Science.gov (United States)

    Mosslemin, Mohammad Hossein; Nateghi, Mohammad Reza

    2010-01-01

    Some fused heterocyclic pyrimidines have been synthesized in high yields using ultrasound irradiation in a one-pot, three-component and efficient process by condensation reaction of barbituric acids, aldehydes and a series of enamines in water. Prominent among the advantages of this new method are operational simplicity, good yields in short reaction times and easy work-up procedures employed.

  16. Removal of pyrimidine dimers in UV-irradiated spores of Dictyostelium discoideum during germination

    Energy Technology Data Exchange (ETDEWEB)

    Okaichi, K.; Tano, K.; Ohnishi, T.; Nozu, K.

    1985-06-01

    The spores of Dictyostelium discoideum TW-8 (radC) are about twice as sensitive to UV than the parental strain NC-4 spores at a 10% survival level. Ultraviolet irradiation apparently suppressed the emergence of amoebae from swollen TW-8 spores as compared with NC-4 spores, though the conversion of spores into swollen spores was not affected by UV irradiation in either strain. About 85% removal of pyrimidine dimers was detected in UV-irradiated NC-4 spores at 200 J/m/sup 2/ during spore germination for 9 h, but no removal of pyrimidine dimers was detected in TW-8 spores under the same conditions. The removal of pyrimidine dimers from the NC-4 spores began at around 2 h germination when the spores have become swollen. The number of enzyme-sensitive sites (ESS) detected by Micrococcus luteus endonuclease in the DNA of UV-irradiated NC-4 spores also began to decrease at about 2 h into germination. The decrease in ESS, however, was hardly detectable in UV-irradiated TW-8 spores at any step during germination. Cycloheximide inhibited both decrease in the number of pyrimidine dimers, and decrease in the number of ESS of UV-irradiated NC-4 spores. It is suggested that UV-specific endonuclease is newly synthesized in swollen spores of NC-4. (author).

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

    Science.gov (United States)

    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.

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

    Directory of Open Access Journals (Sweden)

    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.

  19. Inhibition of pyrimidine biosynthesis pathway suppresses viral growth through innate immunity.

    Directory of Open Access Journals (Sweden)

    Marianne Lucas-Hourani

    Full Text Available Searching for stimulators of the innate antiviral response is an appealing approach to develop novel therapeutics against viral infections. Here, we established a cell-based reporter assay to identify compounds stimulating expression of interferon-inducible antiviral genes. DD264 was selected out of 41,353 compounds for both its immuno-stimulatory and antiviral properties. While searching for its mode of action, we identified DD264 as an inhibitor of pyrimidine biosynthesis pathway. This metabolic pathway was recently identified as a prime target of broad-spectrum antiviral molecules, but our data unraveled a yet unsuspected link with innate immunity. Indeed, we showed that DD264 or brequinar, a well-known inhibitor of pyrimidine biosynthesis pathway, both enhanced the expression of antiviral genes in human cells. Furthermore, antiviral activity of DD264 or brequinar was found strictly dependent on cellular gene transcription, nuclear export machinery, and required IRF1 transcription factor. In conclusion, the antiviral property of pyrimidine biosynthesis inhibitors is not a direct consequence of pyrimidine deprivation on the virus machinery, but rather involves the induction of cellular immune response.

  20. An efficient and green preparation of 5-aminophosphonate substituted pyrimidine nucleosides under solvent-free conditions

    Institute of Scientific and Technical Information of China (English)

    Xin Ying Zhang; Ying Ying Qu; Xue Sen Fan

    2010-01-01

    An environmentally benign and highly efficient one-pot preparation of α-aminophosphonates under solvent-free conditions was developed.By employing this method,5-aminophosphonate substituted pyrimidine nucleosides were synthesized in good to excellent yields starting from 5-formyl-2'-deoxyuridine,aniline and dimethylphosphite.

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

    Directory of Open Access Journals (Sweden)

    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.

  2. Antimicrobial activity of new 4,6-disubstituted pyrimidine, pyrazoline, and pyran derivatives.

    Science.gov (United States)

    Ramiz, Mahmoud M M; El-Sayed, Wael A; El-Tantawy, Asmaa I; Abdel-Rahman, Adel A-H

    2010-05-01

    A number of new 2,6-didisubstituted pyrimidine, pyrazoline, and pyran derivatives were synthesized starting from their chalcone derivative. The synthesized compounds displayed different degrees of antimicrobial activity against Bscillus subtilis (Gram-positive), Pseudomonas aeruginosa (Gram-negative), and Streptomyces species (Actinomycetes).

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

    Energy Technology Data Exchange (ETDEWEB)

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

    DEFF Research Database (Denmark)

    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...

  5. Inwerking van stikstofhoudende nucleofielen op enige 15N-gemerkte pyrimidine- en chinazolinederivaten

    NARCIS (Netherlands)

    Kroon, A.P.

    1974-01-01

    In this thesis an investigation is described on the mechanism of aminations of pyrimidine- and quinazoline derivatives with nitrogen containing bases.In the introduction a survey is given of investigations, reported in the literature, concerning σ-complex formation on azahetarenes and their derivati

  6. Incorporation and Degradation of 14C and 3H-labeled Thymidine by Sugarcane Cells in Suspension Culture 12

    Science.gov (United States)

    Lesley, Stanley M.; Maretzki, Andrew; Nickell, Louis G.

    1980-01-01

    Sugarcane cells growing in suspension culture degrade exogenous thymidine, releasing thymine. Thymine is not utilized for DNA synthesis. Thymine is rapidly catabolized to β-aminoisobutyric acid which is found within the cell. Thymidine in the medium is used for DNA synthesis. The label of [2-14C]thymidine is lost as 14CO2, but the label of [3H]methylthymidine is found in the cell as [3H]β-aminoisobutyric acid, some of which is used for the synthesis of other cell components. The degradation of thymidine can be partially inhibited by addition of certain substituted pyrimidines. PMID:16661365

  7. The enzymology of cytosolic pyrimidine 5'-nucleotidases: functional analysis and physiopathological implications.

    Science.gov (United States)

    Magni, Giulio; Amici, Adolfo; Orsomando, Giuseppe

    2013-01-01

    In mammals, cellular 5'-nucleotidase (5'-NT) activity (EC 3.1.3.5) encompasses a number of genetically and structurally distinct enzyme forms, either membrane-bound or soluble, mainly cytosolic, that are characterized by broad specificity towards nucleoside 5'-monophosphate substrates differing in base (purine/pyrimidine) and/or sugar (oxy/deoxy-ribose) moieties. In particular, among the cytosolic 5'-NTs active towards pyrimidine nucleotides are cN-III and cdN, ubiquitously distributed in mammalian tissues and treated as a single entity in the early days. cN-III was first linked to a genetic defect , hereditary pyrimidine nucleotidase deficiency, associated to a nonspherocyt ic hemolytic anemia disorder of still unclear mechanism but metabolically characterized by abnormally high levels of pyrimidine compounds and ribonucleoproteins in erythrocytes, as evidenced by occurrence of basophilic stippling on blood smearings. Since the first review on pyrimidine-specific nucleotidases (Amici, A.; Magni, G., Arch. Biochem. Biophys., 2002, 397(2), 184- 190), excellent overviews on the topic appeared in the literature. In the present contribution, the major findings on these two enzymatic proteins, cN-III and cdN, will be described with particular emphasis on the relationships between their structure and function, as well as on their roles in normal and pathological conditions. The catalytic mechanism of both specific hydrolytic and phosphotransferase activities, possessed by both enzymes, will be discussed also in the light of recent solution of both cN-III and cdN three-dimensional structures. This review also focuses on possible therapeutic approaches involving cellular 5'-NTs in detoxifying common antiviral and antineoplastic drugs.

  8. Medicinal attributes of pyrazolo[1,5-a]pyrimidine based scaffold derivatives targeting kinases as anticancer agents

    Directory of Open Access Journals (Sweden)

    Nasser S.M. Ismail

    2016-12-01

    Full Text Available Pyrazolo pyrimidines are fused heterocyclic ring systems which known as bioisosteres of adenine, that are necessary for every aspect of cell life. Pyrazolo[1,5-a]pyrimidines derivatives have been explored for their inhibitory activity towards a variety of protein kinase enzymes and their function as anticancer agents. This review to the best of our knowledge is the first assemblage on synthesis and medicinal aspects including structure activity relationships of pyrazolo[1,5-a]pyrimidines reported to date.

  9. Powerful methods to establish chromosomal markers in Lactococcus lactis: an analysis of pyrimidine salvage pathway mutants obtained by positive selections

    DEFF Research Database (Denmark)

    Martinussen, Jan; Hammer, Karin

    1995-01-01

    phosphoribosyltransferase (upp), uridindcytidine kinase (udk), pyrimidine nucleoside phosphorylase (pdp), cytidine/deoxycytidine deaminase (dd), thymidine kinase (tdk) and purine nucleoride phosphorylase (pup). Based on an analysis of the mutants obtained, the pathways by which L. lactis metabolizes uracil...

  10. Simple approach to thieno[3,2-d]pyrimidines as new scaffolds of antimicrobial activities

    Directory of Open Access Journals (Sweden)

    Hafez Hend N.

    2016-09-01

    Full Text Available 6ʹ-(4-Chlorophenyl-spiro[cyclohexane-1,2ʹ-thieno[3,2-d][1,3] oxazin]-4ʹ(1ʹH-one (1 was synthesized and used as a starting material for the synthesis of a novel series of spiro compounds having biologically active sulfonamide 2a-e and 3ʹ-(4-acetylphenyl-6ʹ- (4-chlorophenyl-1ʹH-spiro[cyclohexane-1,2ʹ-thieno[3,2-d] pyrimidine-4ʹ(3ʹH-one (3. Compound 2a was used as a key intermediate for the synthesis of sulfonyl carbothioamide derivatives 4a-c. Also, compound 3 was used as an intermediate for the synthesis of 3ʹH-spiro[cyclohexane-1,2ʹ-thieno[3,2-d]pyrimidin]-3ʹ-yl] phenyl}-2-imino-4-(substituted phenyl and/or thienyl-1,2-dihydropyridine- 3-carbonitrile derivatives 5a-e, 3ʹH-spiro[cyclohexane- 1,2ʹ- thieno[3,2-d]pyrimidin]-3ʹ-yl]phenyl}-2-oxo-4-(substituted phenyl and/or thienyl-1,2-dihydropyridine-3-carbonitrile derivatives 6a-e, and 4-[(2Z-3-substituted-arylprop-2-enoyl] phenyl-1ʹH-spiro[cyclohexane-1,2ʹ-thieno[3,2-d]pyrimidine derivatives 7a-e. Cyclocondensation of 7a-e with hydrazine hydrate produced 6ʹ-(4-chlorophenyl-3ʹ-[4-(5-substituted aryl-4,5-dihydro- 1H-pyrazol-3-ylphenyl]-1ʹH-spiro[cyclohexane-1,2ʹ-thieno- [3,2-d]pyrimidin]-4ʹ(3ʹH-ones 8a-e but with hydroxylamine hydrochloride afforded the corresponding isoxazoline derivatives 9a-e. Also, cyclocondensation by thiourea afforded 2-thioxo-1,2- dihydropyrimidin-4-yl-phenyl-spiro-{cyclohexanethieno[3,2-d] pyrimidin}-4-one derivatives 10a-e. The new compounds were investigated for antimicrobial activity. Compounds 2c, 8b,c, 9b and 10b were the most potent ones against both Gram-negative and Gram-positive bacteria. Compound 8c exhibited higher antifungal activity towards the examined fungi with MIC of 1-2 μmol mL-1 compared to ketoconazole (MIC 2-3 μmol mL-1 .

  11. CEST theranostics: label-free MR imaging of anticancer drugs

    Science.gov (United States)

    Xu, Jiadi; Yadav, Nirbhay N.; Chan, Kannie W. Y.; Luo, Liangping; McMahon, Michael T.; Vogelstein, Bert; van Zijl, Peter C.M.; Zhou, Shibin; Liu, Guanshu

    2016-01-01

    Image-guided drug delivery is of great clinical interest. Here, we explored a direct way, namely CEST theranostics, to detect diamagnetic anticancer drugs simply through their inherent Chemical Exchange Saturation Transfer (CEST) MRI signal, and demonstrated its application in image-guided drug delivery of nanoparticulate chemotherapeutics. We first screened 22 chemotherapeutic agents and characterized the CEST properties of representative agents and natural analogs in three major categories, i.e., pyrimidine analogs, purine analogs, and antifolates, with respect to chemical structures. Utilizing the inherent CEST MRI signal of gemcitabine, a widely used anticancer drug, the tumor uptake of the i.v.-injected, drug-loaded liposomes was successfully detected in CT26 mouse tumors. Such label-free CEST MRI theranostics provides a new imaging means, potentially with an immediate clinical impact, to monitor the drug delivery in cancer. PMID:26837220

  12. Pesticide Product Label System

    Data.gov (United States)

    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...

  13. Food Label and You

    Medline Plus

    Full Text Available ... has issued final changes to update the Nutrition Facts label for packaged foods. For more information, see Changes to the Nutrition Facts Label . FDA presents an entertaining and educational tool ...

  14. Semiotic labelled deductive systems

    Energy Technology Data Exchange (ETDEWEB)

    Nossum, R.T. [Imperial College of Science, Technology and Medicine, London (United Kingdom)

    1996-12-31

    We review the class of Semiotic Models put forward by Pospelov, as well as the Labelled Deductive Systems developed by Gabbay, and construct an embedding of Semiotic Models into Labelled Deductive Systems.

  15. Electronic Submission of Labels

    Science.gov (United States)

    Pesticide registrants can provide draft and final labels to EPA electronically for our review as part of the pesticide registration process. The electronic submission of labels by registrants is voluntary but strongly encouraged.

  16. Mental Labels and Tattoos

    Science.gov (United States)

    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)

  17. A Label to Regulate

    DEFF Research Database (Denmark)

    Tricoire, Aurélie; Boxenbaum, Eva; Laurent, Brice

    This paper examines the role labelling plays in the government of the contemporary economy.1Drawing on a detailed study of BBC-Effinergy, a French label for sustainable construction, we showhow the adoption and evolution of voluntary labels can be seen as emblematic of a governmentthrough experim...... experiment engaging 4 operations: stimulating market anticipations, focussing politicalconsultations, producing collective expertise and containing the regulatory transcription of the label....

  18. Synthesis, and Fluorescence Properties of Coumarin and Benzocoumarin Derivatives Conjugated Pyrimidine Scaffolds for Biological Imaging Applications.

    Science.gov (United States)

    Al-Masoudi, Najim A; Al-Salihi, Niran J; Marich, Yossra A; Markus, Timo

    2015-11-01

    Series of coumarin and 5,6-benzomcomarin substituted pyrimidine derivatives 11-15 and 22-25 were synthesized, aiming to develop new imaging fluorescent agents. Analogously, treatment of 4-chloropyrimidine analog 16 with coumarin 3-carbohyrazide 5 under MWI condition followed by boiling with NH4OAc in HOAc furnished coumarin-1,2,4-triazolo-pyrimidine analog 18. The fluorescence property was investigated spectrophotometrically in MeOH with Rhodamine 6G as standard dye. All the compounds showed emission in the region between 331 and 495 nm. The quantum yield of all the compounds were found to be weak, except methyl benzocoumarin 3-carboxylate 22 which showed (ΦF = 0.98) in comparison to Rhodamine 6G as standard (ΦF = 0.95).

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

  20. The effect of purine and pyrimidine analogues and virazole on adenovirus replication.

    Science.gov (United States)

    Scheffler, P; Haghchenas, D; Wigand, R

    1975-04-01

    The multiplication of adenovirus 19 in HeLa cells was inhibited by various purine and pyrimidine analogues and by virazole. The formation of infectious virus and of capsid proteins (haemagglutin, group-specific complement-fixing antigen) was inhibited to the same degree, while the viral cytopathic effect (CPE) was not inhibited. The reversibility of the inhibition after removal of the substances was more complete for purine than for pyrimidine analogues. The inhibition was counteracted by simulataneous addition of the corresponding nucleosides. Adenosine was more effected than guanosine against purine analogues; both were partially effective against virazole, but none of them against arabinofuranosyladenine. The time-dependence of inhibition, the ensuing eclipse period after removal of the inhibitors, and the successive application of two inhibitors led to the conclusion that most of them affect the viral multiplication mainly by inhibition of DNA synthesis. Azacytidine inhibits the synthesis of structural proteins as well.

  1. Direct Isolation of Purines and Pyrimidines from Nucleic Acids Using Sublimation

    Science.gov (United States)

    Glavin, Daniel P.; Schubert, Michael; Bada, Jeffrey L.

    2003-01-01

    A sublimation technique was developed to isolate purines and pyrimidines directly from lambda-deoxyribonucleic acid (lambda-DNA) and Escherichia coli cells. The sublimation of adenine, cytosine, guanine, and thymine from lambda-DNA was tested under reduced pressure (approx. 0.5 Torr) at temperatures of >150 C. With the exception of guanine, approximately 60 -75% of each base was sublimed directly from the lambda-DNA and recovered on a coldfinger of the sublimation apparatus after heating to 450 C. Several nucleobases including adenine, cytosine, thymine, and uracil were also recovered from E. coli bacteria after heating the cells to the same temperature, although some thermal decomposition of the bases also occurred. These results demonstrate the feasibility of using sublimation to isolate purines and pyrimidines from native E. coli DNA and RNA without any chemical treatment of the cells.

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

    Directory of Open Access Journals (Sweden)

    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.

  3. 3-({5-Bromo-4-[pyrrolidin-1-yl]pyrimidin-2-yl}aminophenol

    Directory of Open Access Journals (Sweden)

    Alan M. Jones

    2015-05-01

    Full Text Available Re-investigation of the 1H-NMR spectrum reported for 15-bromo-4-oxa-2,9-diaza-1(2,4-pyrimidine-3(1,3-benzenacyclononaphane (2 prepared via a Mitsunobu- mediated macroether cyclisation led to a proposed structural isomer (3. The title compound (3 was prepared via a two-step protocol and assigned using 1H, 13C-NMR and LC-MS.

  4. A Facile Microwave-Assisted Synthesis of Some Fused Pyrimidine Derivatives

    Directory of Open Access Journals (Sweden)

    S. A. Al-Issa

    2014-06-01

    Full Text Available The highly accelerated synthesis of thienopyrimidinones, theino- pyrimidines,thioxotheinopyrimidinones and a thienotriazolopyrimidinone derivatives under microwave irradiation is reported. Compared to conventional conditions, microwaves method offered several advantage likes short time, good yields, simple procedure, mild conditions and easy workup. The structure of synthesized compounds have been characterized on the basis of their elemental analysis and spectral data, and screened for their antimicrobial activity.

  5. Diversion of aspartate in ASS1-deficient tumours fosters de novo pyrimidine synthesis.

    Science.gov (United States)

    Rabinovich, Shiran; Adler, Lital; Yizhak, Keren; Sarver, Alona; Silberman, Alon; Agron, Shani; Stettner, Noa; Sun, Qin; Brandis, Alexander; Helbling, Daniel; Korman, Stanley; Itzkovitz, Shalev; Dimmock, David; Ulitsky, Igor; Nagamani, Sandesh C S; Ruppin, Eytan; Erez, Ayelet

    2015-11-19

    Cancer cells hijack and remodel existing metabolic pathways for their benefit. Argininosuccinate synthase (ASS1) is a urea cycle enzyme that is essential in the conversion of nitrogen from ammonia and aspartate to urea. A decrease in nitrogen flux through ASS1 in the liver causes the urea cycle disorder citrullinaemia. In contrast to the well-studied consequences of loss of ASS1 activity on ureagenesis, the purpose of its somatic silencing in multiple cancers is largely unknown. Here we show that decreased activity of ASS1 in cancers supports proliferation by facilitating pyrimidine synthesis via CAD (carbamoyl-phosphate synthase 2, aspartate transcarbamylase, and dihydroorotase complex) activation. Our studies were initiated by delineating the consequences of loss of ASS1 activity in humans with two types of citrullinaemia. We find that in citrullinaemia type I (CTLN I), which is caused by deficiency of ASS1, there is increased pyrimidine synthesis and proliferation compared with citrullinaemia type II (CTLN II), in which there is decreased substrate availability for ASS1 caused by deficiency of the aspartate transporter citrin. Building on these results, we demonstrate that ASS1 deficiency in cancer increases cytosolic aspartate levels, which increases CAD activation by upregulating its substrate availability and by increasing its phosphorylation by S6K1 through the mammalian target of rapamycin (mTOR) pathway. Decreasing CAD activity by blocking citrin, the mTOR signalling, or pyrimidine synthesis decreases proliferation and thus may serve as a therapeutic strategy in multiple cancers where ASS1 is downregulated. Our results demonstrate that ASS1 downregulation is a novel mechanism supporting cancerous proliferation, and they provide a metabolic link between the urea cycle enzymes and pyrimidine synthesis.

  6. Photoreactivation of pyrimidine dimers in DNA from thyroid cells of the teleost, Poecilia formosa

    Energy Technology Data Exchange (ETDEWEB)

    Achey, P.M.; Woodhead, A.D.; Setlow, R.B.

    1979-01-01

    We have developed and used a simple technique to estimate the quantity of pyrimidine dimers in unlabeled cellular DNA. DNA is extracted from cells, treated with an endonuclease specific for dimers, and its molecular weight estimated by its electrophoretic mobility on alkaline agarose slab gels. The technique is used to show that cells from thyroid tissue of the fish Poecilia formosa have photoreactivating activity towards dimmers in the cellular DNA.

  7. Dichloridobis[2-methyl-sulfanyl-4-(pyridin-2-yl)pyrimidine-κN,N]cobalt(II).

    Science.gov (United States)

    Yang, Wen-Na

    2011-09-01

    The asymmetric unit of the title compound, [CoCl(2)(C(10)H(9)N(3)S)(2)], contains one half-mol-ecule with the Co(II) atom situtated on a twofold rotational axis. The Co(II) atom, in an octa-hedral enviroment, is coordinated by four N atoms from two 2-methyl-sulfanyl-4-(pyridin-2-yl)pyrimidine ligands and two Cl atoms.

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

  9. Labeling Schemes with Queries

    OpenAIRE

    2006-01-01

    We study the question of ``how robust are the known lower bounds of labeling schemes when one increases the number of consulted labels''. Let $f$ be a function on pairs of vertices. An $f$-labeling scheme for a family of graphs $\\cF$ labels the vertices of all graphs in $\\cF$ such that for every graph $G\\in\\cF$ and every two vertices $u,v\\in G$, the value $f(u,v)$ can be inferred by merely inspecting the labels of $u$ and $v$. This paper introduces a natural generalization: the notion of $f$-...

  10. Fluorescent property of 3-hydroxymethyl imidazo[1,2-a]pyridine and pyrimidine derivatives

    Directory of Open Access Journals (Sweden)

    Velázquez-Olvera Stephania

    2012-08-01

    Full Text Available Abstract Background Imidazo[1,2-a]pyridines and pyrimidines are important organic fluorophores which have been investigated as biomarkers and photochemical sensors. The effect on the luminescent property by substituents in the heterocycle and phenyl rings, have been studied as well. In this investigation, series of 3-hydroxymethyl imidazo[1,2-a]pyridines and pyrimidines were synthesized and evaluated in relation to fluorescence emission, based upon the hypothesis that the hydroxymethyl group may act as an enhancer of fluorescence intensity. Results Compounds of both series emitted light in organic solvents dilutions as well as in acidic and alkaline media. Quantitative fluorescence spectroscopy determined that both fused heterocycles fluoresced more intensely than the parent unsubstituted imidazo[1,2-a]azine fluorophore. In particular, 3-hydroxymethyl imidazo[1,2-a]pyridines fluoresced more intensely than 3-hydroxymethyl imidazo[1,2-a]pyrimidines, the latter emitting blue light at longer wavelengths, whereas the former emitted purple light. Conclusion It was concluded that in most cases the hydroxymethyl moiety did act as an enhancer of the fluorescence intensity, however, a comparison made with the fluorescence emitted by 2-aryl imidazo[1,2-a]azines revealed that in some cases the hydroxymethyl substituent decreased the fluorescence intensity.

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

  12. Isolation of Purines and Pyrimidines from the Murchison Meteorite Using Sublimation

    Science.gov (United States)

    Glavin, D. P.; Bada, J. L.

    2004-01-01

    The origin of life on Earth, and possibly on other planets such as Mars, would have required the presence of liquid water and a continuous supply of prebiotic organic compounds. The exogenous delivery of organic matter by asteroids, comets, and carbonaceous meteorites could have contributed to the early Earth s prebiotic inventory by seeding the planet with biologically important organic compounds. A wide variety of prebiotic organic compounds have previously been detected in the Murchison CM type carbonaceous chondrite including amino acids, purines and pyrimidines. These compounds dominate terrestrial biochemistry and are integral components of proteins, DNA and RNA. Several purines including adenine, guanine, hypoxanthine, and xanthine, as well as the pyrimidine uracil, have previously been detected in water or formic acid extracts of Murchison using ion-exclusion chromatography and ultraviolet spectroscopy. However, even after purification of these extracts, the accurate identification and quantification of nucleobases is difficult due to interfering UV absorbing compounds. In order to reduce these effects, we have developed an extraction technique using sublimation to isolate purines and pyrimidines from other non-volatile organic compounds in Murchison acid extracts.

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

  14. Purine and pyrimidine metabolism: Convergent evidence on chronic antidepressant treatment response in mice and humans

    Science.gov (United States)

    Park, Dong Ik; Dournes, Carine; Sillaber, Inge; Uhr, Manfred; Asara, John M.; Gassen, Nils C.; Rein, Theo; Ising, Marcus; Webhofer, Christian; Filiou, Michaela D.; Müller, Marianne B.; Turck, Christoph W.

    2016-01-01

    Selective Serotonin Reuptake Inhibitors (SSRIs) are commonly used drugs for the treatment of psychiatric diseases including major depressive disorder (MDD). For unknown reasons a substantial number of patients do not show any improvement during or after SSRI treatment. We treated DBA/2J mice for 28 days with paroxetine and assessed their behavioral response with the forced swim test (FST). Paroxetine-treated long-time floating (PLF) and paroxetine-treated short-time floating (PSF) groups were stratified as proxies for drug non-responder and responder mice, respectively. Proteomics and metabolomics profiles of PLF and PSF groups were acquired for the hippocampus and plasma to identify molecular pathways and biosignatures that stratify paroxetine-treated mouse sub-groups. The critical role of purine and pyrimidine metabolisms for chronic paroxetine treatment response in the mouse was further corroborated by pathway protein expression differences in both mice and patients that underwent chronic antidepressant treatment. The integrated -omics data indicate purine and pyrimidine metabolism pathway activity differences between PLF and PSF mice. Furthermore, the pathway protein levels in peripheral specimens strongly correlated with the antidepressant treatment response in patients. Our results suggest that chronic SSRI treatment differentially affects purine and pyrimidine metabolisms, which may explain the heterogeneous antidepressant treatment response and represents a potential biosignature. PMID:27731396

  15. Advancing viral RNA structure prediction: measuring the thermodynamics of pyrimidine-rich internal loops.

    Science.gov (United States)

    Phan, Andy; Mailey, Katherine; Sakai, Jessica; Gu, Xiaobo; Schroeder, Susan J

    2017-02-17

    Accurate thermodynamic parameters improve RNA structure predictions and thus accelerate understanding of RNA function and the identification of RNA drug binding sites. Many viral RNA structures, such as internal ribosome entry sites, have internal loops and bulges that are potential drug target sites. Current models used to predict internal loops are biased towards small, symmetric purine loops, and thus poorly predict asymmetric, pyrimidine-rich loops with more than 6 nucleotides that occur frequently in viral RNA. This paper presents new thermodynamic data for 40 pyrimidine loops, many of which can form UU or protonated CC base pairs. Protonated cytosine and uracil base pairs stabilize asymmetric internal loops. Accurate prediction rules are presented that account for all thermodynamic measurements of RNA asymmetric internal loops. New loop initiation terms for loops with more than 6 nucleotides are presented that do not follow previous assumptions that increasing asymmetry destabilizes loops. Since the last 2004 update, 126 new loops with asymmetry or sizes greater than 2x2 have been measured (Mathews 2004). These new measurements significantly deepen and diversify the thermodynamic database for RNA. These results will help better predict internal loops that are larger, pyrimidine-rich, and occur within viral structures such as internal ribosome entry sites.

  16. SYNTHESIS AND BIOLOGICAL ACTIVITY OF IMIDAZOLE DERIVED CHALCONES AND IT’S PYRIMIDINES

    Directory of Open Access Journals (Sweden)

    Pavan Kumar Padarthi

    2013-06-01

    Full Text Available Microbial contribution increasing rapidly due to invasion by the pathogenic organisms like bacteria, fungi and virus in the present disease burden of human health. To treat these diseases many potent and broad spectrum antibiotics were discovered e.g., ampicillin, amoxicillin, carbenicillin, ofloxacin and tetracycline etc., Even though antibiotics are life saving drugs in therapeutics but they are potentially harmful. These harmful effects include allergic and anaphylactic reaction, development of resistance, destruction of normal non-pathogenic bacterial flora and selective toxicity like aplastic anemia, kidney damage. As the microbial resistance make anti-microbial therapy very complex, there is a definite need of novel anti-microbials or drugs for combination therapy with standard antibiotics. Our aim was to synthesize and explore the anti-microbial activity of chalcones and its derived pyrimidines against various pathological micro organisms. Novel imidazole derived chalcones were synthesized and characterization was carried out by analyzing melting point, IR, 1H NMR data. The synthesized chalcones and pyrimidines are tested for their antimicrobial activity against various bacteria as well as fungi. Further synthesis of novel heterocyclic chalcones, structural elucidation, spectral analysis, biological activity of synthesized chalcones and its derived pyrimidines gives a hope for enhanced biological action using QSAR Studies.

  17. Rim2, a pyrimidine nucleotide exchanger, is needed for iron utilization in mitochondria

    Science.gov (United States)

    Yoon, Heeyong; Zhang, Yan; Pain, Jayashree; Lyver, Elise R.; Lesuisse, Emmanuel; Pain, Debkumar; Dancis, Andrew

    2016-01-01

    Mitochondria transport and utilize iron for the synthesis of haem and Fe–S clusters. Although many proteins are known to be involved in these processes, additional proteins are likely to participate. To test this hypothesis, in the present study we used a genetic screen looking for yeast mutants that are synthetically lethal with the mitochondrial iron carriers Mrs3 and Mrs4. Several genes were identified, including an isolate mutated for Yfh1, the yeast frataxin homologue. All such triple mutants were complemented by increased expression of Rim2, another mitochondrial carrier protein. Rim2 overexpression was able to enhance haem and Fe–S cluster synthesis in wild-type or Δmrs3/Δmrs4 backgrounds. Conversely Rim2 depletion impaired haem and Fe–S cluster synthesis in wild-type or Δmrs3/Δmrs4 backgrounds, indicating a unique requirement for this mitochondrial transporter for these processes. Rim2 was previously shown to mediate pyrimidine exchange in and out of vesicles. In the present study we found that isolated mitochondria lacking Rim2 exhibited concordant iron defects and pyrimidine transport defects, although the connection between these two functions is not explained. When organellar membranes were ruptured to bypass iron transport, haem synthesis from added iron and porphyrin was still markedly deficient in Rim2-depleted mitochondrial lysate. The results indicate that Rim2 is a pyrimidine exchanger with an additional unique function in promoting mitochondrial iron utilization. PMID:21777202

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

    Science.gov (United States)

    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.

  19. T-lymphocytes from AIDS patients are unable to synthesize ribonucleotides de novo in response to mitogenic stimulation. Impaired pyrimidine responses are already evident at early stages of HIV-1 infection.

    Science.gov (United States)

    Bofill, M; Fairbanks, L D; Ruckemann, K; Lipman, M; Simmonds, H A

    1995-12-15

    Proliferative defects have been reported at the level of DNA synthesis, even in T-lymphocytes from asymptomatic human immunodeficiency virus type-1+ (HIV-1+) patients. Since purine and pyrimidine ribonucleotide availability is crucial for proliferation, we compared the ability of HIV-1- and HIV-1+ T-lymphocytes (> 95% CD4+ and CD8+) to activate de novo biosynthetic and salvage pathways following phytohemagglutinin stimulation using 14C-labeled precursors. The striking abnormality already detectable in asymptomatic patients' cells was the impaired ability of CTP, UDP-Glc, and UTP pools to expand over 72 h (44-70% of control), although ATP and GTP pools and responses were normal. In symptomatic patients, resting T-cells showed markedly reduced pyrimidine pools (53-74% of control) with no change following activation. Relatively normal ATP, GTP, and NAD pools masked the same impaired response of de novo synthesis to activation, with ATP and GTP being reduced by 50% at 48 h. Purine salvage was more active than the control in unstimulated HIV-1+ cells. This impaired de novo synthesis in HIV-1+ T-lymphocytes severely restricts the availability of ribonucleotides for vital growth-related activities such as membrane expansion and strand break repair as well as DNA and RNA synthesis. The data indicate that resting T-lymphocytes from symptomatic patients survive through enhanced salvage, but the stimulation induces metabolic cell death, and provide an explanation for the activation-associated lymphocyte death seen in HIV-1+ T-lymphocytes.

  20. Succesful labelling schemes

    DEFF Research Database (Denmark)

    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 ......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...... it into consideration when I go shopping. The respondent was asked to pick the most suitable answer, which described her use of each label. 29% - also called 'the labelling blind' - responded that they basically only knew the recycling label and the Government controlled organic label 'Ø-mærket'. Another segment of 6...

  1. Synthesis and Antimicrobial Activity of Some New Pyrazole, Fused Pyrazolo[3,4-d]-pyrimidine and Pyrazolo[4,3-e][1,2,4]- triazolo[1,5-c]pyrimidine Derivatives

    Directory of Open Access Journals (Sweden)

    Omar A. Miqdad

    2008-07-01

    Full Text Available Hydrazonyl bromides 2a,b reacted with active methylene compounds (dibenzoylmethane, acetylacetone, ethyl acetoacetate, phenacyl cyanide, acetoacetanilide, ethyl cyanoacetate, cyanoacetamide and malononitrile to afford the corresponding 1,3,4,5- tetrasubstituted pyrazole derivatives 5-12a,b. Reaction of 12a,b with formamide, formic acid and triethyl orthoformate give the pyrazolo[3,4-d]pyrimidine, pyrazolo[3,4- d]pyrimidin-4(3Hone and 5-ethoxymethylene-aminopyrazole-4-carbo-nitrile derivatives 13-15a,b, respectively. Compounds 15a,b reacted with benzhydrazide and hydrazine hydrate to afford pyrazolo[4,3-e][1,2,4]triazolo[1,5-c]pyrimidine and [4-iminopyrazolo- [3,4-d]pyrimidin-5-yl]amine derivatives 16a,b and 17a,b. Reactions of compounds 17a,b with triethyl orthoformate and carbon disulfide give the corresponding pyrazolo[4,3-e]- [1,2,4]triazolo[1,5-c]pyrimidine derivatives 18a,b and 19a,b, respectively.

  2. HPLC analysis for the clinical-biochemical diagnosis of inborn errors of metabolism of purines and pyrimidines.

    Science.gov (United States)

    Lazzarino, Giuseppe; Amorini, Angela Maria; Di Pietro, Valentina; Tavazzi, Barbara

    2011-01-01

    The determination of purines and pyrimidines in biofluids is useful for the clinical-biochemical characterization of acute and chronic pathological states that induce transient or permanent alterations of metabolism. In particular, the diagnosis of several inborn errors of metabolism (IEMs) is accomplished by the analysis of circulating and excreted purines and pyrimidines. It is certainly advantageous to simultaneously determine the full purine and pyrimidine profile, as well as to quantify other compounds of relevance (e.g., organic acids, amino acids, sugars) in various metabolic hereditary diseases, in order to screen for a large number of IEMs using a reliable and sensitive analytical method characterized by mild to moderate costs. Toward this end, we have developed an ion-pairing HPLC method with diode array detection for the synchronous separation of several purines and pyrimidines. This method also allows the quantification of additional compounds such as N-acetylated amino acids and dicarboxylic acids, the concentrations of which are profoundly altered in different IEMs. The application of the method in the analysis of biological samples from patients with suspected purine and pyrimidine disorders is presented to illustrate its applicability for the clinical-biochemical diagnosis of IEM.

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Science.gov (United States)

    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.

  6. Potential radiosensitizing antiviral and anticancer pyrimidine nucleosides. Technical progress report, June 1, 1975--December 22, 1975. [UV radiation

    Energy Technology Data Exchange (ETDEWEB)

    Prusoff, W.H.

    1976-01-01

    A newly developed method of synthesis now affords the large scale production of 5'-amino analogs of a variety of nucleosides. This procedure has been used to synthesize the 5'-amino analog of 5-iodo-, 5-bromo-, 5-chloro-, 5-fluoro-, 5-trifluoromethyl-2',5'-dideoxyuridine. In addition to the previously established antiviral activity of 5-iodo-5'-amino-2',5'-dideoxyuridine (AIU), we have found 5-bromo- (ABrU) and 5-iodo-5'-amino-2',5'-dideoxycytidine (AIC) to be even more potent antiviral agents than AIU both in vitro and of AIC against experimental herpatic keratitis in rabbits. Initial studies indicate a non-toxicity in vitro. There is sound reason to predict AIC and ABrC to each have a broader spectrum of antiviral activity than AIU and to have a similar lack of toxicity. 5-Fluoro- as well as 5-trifluoromethyl-5'-amino-2',5'-dideoxyuridine, and 5'-amino arabinosyl cytosine (A-ara C) have antiviral activity which is less potent than the parent compound, but each has a vastly improved therapeutic index. Additional experiments have been performed with experimental herpetic keratitis which confirm that AIU has similar efficacy but less potency than iododeoxyuridine, however the favorable therapeutic index of AIU should make it a preferable agent. Metabolic studies show AIU to be incorporated into the DNA of only cells infected with herpes simplex virus (HSV) type 1, and to be phosphorylated by a cell-free extract from only HSV infected cells. These findings explain the complete lack of toxicity to the uninfected cell whether in vitro or in vivo.

  7. 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

    Directory of Open Access Journals (Sweden)

    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.

  8. Studies on Synthesis of Some Novel Heterocyclic Chalcone, Pyrazoline, Pyrimidine - 2 - One, Pyrimidine - 2 - Thione, para-Acetanilide Sulphonyl and Benzoyl Derivatives and their Antimicrobial Activity

    Directory of Open Access Journals (Sweden)

    Rakesh N. Mistry

    2005-01-01

    Full Text Available 1, 2 - Dichloro benzene on chlorosulphonation by chlorosulphonic acid gives 1, 2 - [dichloro] - benzene sulphonyl chloride which on condensation with p –amino acetophenone gives 1-[acetyl] - 1’ , 2’ - [dichloro] - dibenz sulphonamide derivative. This derivative undergo condensation with 2,4- dichloro benzaldehyde gives 1- [3” - (sub. phenyl - 2” - propene - 1” - one] - 1’ , 2’ - [dichloro] - dibenz sulphonamide derivative which on reaction with 99% hydrazine hydrate and glacial acetic acid gives 1-[acetyl]-3- [1’ , 2’ - (dichloro - dibenz sulphonamide] -5 - [2” , 4” - dichloro phenyl] - 2 - pyrazoline derivative. This derivative reacts with various substituted aldehydes to give corresponding substituted chalcone derivatives [1(a-j]. Now, these chalcone derivatives [1(a-j] on condensation with urea gives corresponding substituted pyrimidine - 2 - one derivatives [2(a-j] and on condensation with thio-urea gives corresponding substituted pyrimidine- 2 -thione derivatives [3(a-j]. Further, these chalcone derivatives [1(a-j] on reaction with 99% hydrazine hydrate gives 1 - [1’ - (H - 5’ - (sub. phenyl - 2’ - pyrazoline]- 3 - [1” , 2” - (dichloro - dibenz sulphonamide] - 5 - [2’’’ , 4’’’ - dichloro phenyl]-2- pyrazoline derivatives [4(a-j] as an intermediate compounds, which on condensation with p-acetanilide sulphonyl chloride gives corresponding substituted p - acetanilide sulphonyl derivatives [5(a-j] and on condensation with benzoyl chloride gives corresponding substituted benzoyl derivatives [6(a-j]. Structure elucidation of synthesised compounds has been made on the basis of elemental analysis, I.R. spectral studies and 1H N.M.R. spectral studies. The antimicrobial activity of the synthesised compounds has been studied against the cultures “Staphylococcus aureus”, “Escherichia coli” and “Candela albicans”.

  9. An unusual correlation between ppGpp pool size and rate of ribosome synthesis during partial pyrimidine starvation of Escherichia coli

    DEFF Research Database (Denmark)

    Vogel, Ulla; Pedersen, Steen; Jensen, Kaj Frank

    1991-01-01

    Escherichia coli was exposed to partial pyrimidine starvation by feeding a pyrBI strain orotate as the only pyrimidine source. Subsequently, differential rates of synthesis of rRNA and of a few ribosome-associated proteins as well as the pool sizes of nucleoside triphosphates and ppGpp were...

  10. 1-(2-Ethoxyethyl)-1H-pyrazolo[4,3-d]pyrimidines as potent phosphodiesterase 5 (PDE5) inhibitors.

    Science.gov (United States)

    Tollefson, Michael B; Acker, Brad A; Jacobsen, E J; Hughes, Robert O; Walker, John K; Fox, David N A; Palmer, Michael J; Freeman, Sandra K; Yu, Ying; Bond, Brian R

    2010-05-15

    1H-Pyrazolo[4,3-d]pyrimidines are a class of potent and selective second generation phosphodiesterase 5 (PDE5) inhibitors. This work explores the potency, selectivity and efficacy of 1-(2-ethoxyethyl)-1H-pyrazolo[4,5-d]pyrimidines as PDE5 inhibitors resulting in the advancement of a clinical candidate.

  11. Food Label and You

    Medline Plus

    Full Text Available ... En Español Search FDA Submit search Popular Content Home Food Drugs Medical Devices Radiation-Emitting Products Vaccines, Blood & Biologics Animal & Veterinary Cosmetics Tobacco Products Food Home Food Ingredients, Packaging & Labeling Labeling & Nutrition The Food ...

  12. Synthesis and Antimicrobial Activity of some Tetrahydro Quinolone Diones and Pyrano[2,3-d]pyrimidine Derivatives

    Science.gov (United States)

    Shahi, Masoume; Foroughifar, Naser; Mobinikhaledi, Akbar

    2015-01-01

    There has been special interest in the chemistry of quinolone and pyrimidine derivatives due to their diverse biological activities such as anticonvulsant, anti-malarial agents, antibacterial, antiviral, cytostatic, antithelemintic, antigenotoxic, anti-cancer agents. These compounds are also used as targeting delayed-type hypersensivity and anti-convulsant agents. As a part of our research works in the synthesis of pyrimidine derivatives containing biological activities, a series of novel pyrano[2,3-d]pyrimidine derivatives 2 and tetrahydro quinolone dione derivatives 3 were synthesized via reaction of tetrahydrobenzo[b]pyrano derivatives 1 with different reagents in suitable yields. The characterization of these synthesized compounds was established by IR, 1H NMR and 13C NMR spectroscopic data. Furthermore, all compounds were subsequently evaluated for their in-vitro antibacterial activity against three bacteria: Staphylococcus aureus (ATTC-25923), Escherichia Coli (ATTC-25922) and Bacillus anthracic (ATTC-25924). PMID:26330864

  13. The reaction of the acrylonitrile ion CH 2dbnd CH-C tbnd N rad + with HCN: Proton-transport catalysis vs formation of ionized pyrimidine

    Science.gov (United States)

    Ervasti, Henri K.; Jobst, Karl J.; Gerbaux, Pascal; Burgers, Peter C.; Ruttink, Paul J. A.; Terlouw, Johan K.

    2009-11-01

    The CBS-QB3 model chemistry predicts that the title ion-molecule reaction, of potential interest in astrochemistry, yields a stable head-to-tail dimer, [HC dbnd N-CH 2C(H)C tbnd N] rad + ( D1). Cyclization of D1 into ionized pyrimidine seems possible, but the initiating 1,2-H shift is close in energy to back-dissociation into CH 2dbnd C(H)CN rad + ( AN) + HCN. Less energy demanding is formation of the H-bridged isomers [CH 2dbnd C(CN)H--N tbnd CH] rad + and [HC tbnd N--HC(H) dbnd C(H)CN] rad +, whose HCN component may catalyze isomerization of AN into CH 2dbnd C dbnd C dbnd NH rad + ( AN1) and CH dbnd C(H)C dbnd NH rad + ( AN2) respectively. Tandem mass spectrometry based experiments using 15N/ 13C labelling show that cyclization of D1 does not occur and that AN1 is the predominant reaction product instead.

  14. Bis(arylvinyl)pyrazines, -pyrimidines, and -pyridazines as imaging agents for tau fibrils and β-amyloid plaques in Alzheimer's disease models.

    Science.gov (United States)

    Boländer, Alexander; Kieser, Daniel; Voss, Constantin; Bauer, Silvia; Schön, Christian; Burgold, Steffen; Bittner, Tobias; Hölzer, Jana; Heyny-von Haußen, Roland; Mall, Gerhard; Goetschy, Valérie; Czech, Christian; Knust, Henner; Berger, Robert; Herms, Jochen; Hilger, Ingrid; Schmidt, Boris

    2012-11-08

    The in vivo diagnosis of Alzheimer's disease (AD) is of high socioeconomic interest and remains a demanding field of research. The biopathological hallmarks of the disease are extracellular plaques consisting of aggregated β-amyloid peptides (Aβ) and tau protein derived intracellular tangles. Here we report the synthesis and evaluation of fluorescent pyrazine, pyrimidine,and pyridazine derivatives in vitro and in vivo aiming at a tau-based diagnosis of AD. The probes were pre-evaluated on human brain tissue by fluorescence microscopy and were found to label all known disease-related alterations at high contrast and specificity. To quantify the binding affinity, a new thiazine red displacement assay was developed and selected candidates were toxicologically profiled. The application in transgenic mouse models demonstrated bioavailability and brain permeability for one compound. In the course of histological testing, we discovered an AD-related deposition of tau aggregates in the Bowman's glands of the olfactory epithelium, which holds potential for an endoscopic diagnosis of AD in the olfactory system.

  15. A study of the valence shell photoionisation dynamics of pyrimidine and pyrazine

    Energy Technology Data Exchange (ETDEWEB)

    Holland, D.M.P., E-mail: david.holland@stfc.ac.uk [Daresbury Laboratory, Daresbury, Warrington, Cheshire WA4 4AD (United Kingdom); Potts, A.W. [Department of Physics, King' s College, Strand, London WC2R 2LS (United Kingdom); Karlsson, L. [Department of Physics, Uppsala University, Box 530, SE-751 21 Uppsala (Sweden); Stener, M.; Decleva, P. [Dipartimento di Scienze Chimiche, Universita di Trieste, Via L. Giorgieri, I-34127 Trieste (Italy); Consorzio Interuniversitario Nazionale per la Scienze e Tecnologia dei Materiali, INSTM, Unita' di Trieste, Via L. Giorgieri, I-34127 Trieste (Italy); CNR-IOM, Area Science Park - Basovizza, Strada Statale 14 km 163,5, I-34149 Trieste (Italy)

    2011-11-18

    Graphical abstract: The complete valence shell photoelectron spectra of pyrimidine and pyrazine have been recorded with synchrotron radiation and interpreted with the aid of vertical ionisation energies and relative spectral intensities calculated using time-dependent density functional theory. Highlights: Black-Right-Pointing-Pointer Valence shell photoelectron spectra of pyrimidine and pyrazine have been recorded. Black-Right-Pointing-Pointer Many-body effects are important. Black-Right-Pointing-Pointer Photoionisation dynamics are affected by shape resonances. Black-Right-Pointing-Pointer Theoretical predictions for single-hole ionic states are satisfactory. - Abstract: The complete valence shell photoelectron spectra of pyrimidine and pyrazine have been recorded with synchrotron radiation and the observed structure has been interpreted with the aid of vertical ionisation energies and relative spectral intensities calculated using time-dependent density functional theory. The theoretical predictions for the single-hole ionic states due to outer valence shell ionisation agree satisfactorily with the experimental results. Ionisation from the inner valence orbitals is strongly influenced by many-body effects and the intensity associated with a particular orbital is spread amongst numerous satellites. Photoelectron angular distributions and partial cross sections have been determined both experimentally and theoretically, and demonstrate that shape resonances affect the valence shell photoionisation dynamics. In addition to shape resonances occurring a few eV above the ionisation threshold, the calculations indicate that many of the orbitals are influenced by shape resonant processes at much higher energies. Some of these higher energy resonances have been confirmed through a comparison between the relevant theoretical and experimental photoelectron asymmetry parameters. The spectral behaviour of asymmetry parameters associated with {pi}-orbitals has been shown to

  16. Irradiation of pyrimidine in pure H2O ice with high-energy ultraviolet photons.

    Science.gov (United States)

    Nuevo, Michel; Chen, Yu-Jung; Hu, Wei-Jie; Qiu, Jun-Ming; Wu, Shang-Ruei; Fung, Hok-Sum; Chu, Ching-Chi; Yih, Tai-Sone; Ip, Wing-Huen; Wu, C-Y Robert

    2014-02-01

    The detection of nucleobases, the informational subunits of DNA and RNA, in several meteorites suggests that these compounds of biological interest were formed via astrophysical, abiotic processes. This hypothesis is in agreement with recent laboratory studies of irradiation of pyrimidine in H2O-rich ices with vacuum UV photons emitted by an H2-discharge lamp in the 6.9-11.3 eV (110-180 nm) range at low temperature, shown to lead to the abiotic formation of several compounds including the nucleobases uracil, cytosine, and thymine. In this work, we irradiated H2O:pyrimidine ice mixtures under astrophysically relevant conditions (14 K, ≤10(-9) torr) with high-energy UV photons provided by a synchrotron source in three different ranges: the 0(th) order light (4.1-49.6 eV, 25-300 nm), the He i line (21.2 eV, 58.4 nm), and the He ii line (40.8 eV, 30.4 nm). The photodestruction of pyrimidine was monitored with IR spectroscopy, and the samples recovered at room temperature were analyzed with liquid and gas chromatographies. Uracil and its precursor 4(3H)-pyrimidone were found in all samples, with absolute and relative abundances varying significantly from one sample to another. These results support a scenario in which compounds of biological interest can be formed and survive in environments subjected to high-energy UV radiation fields.

  17. Synthesis, solid-state fluorescence properties, and computational analysis of novel 2-aminobenzo[4,5]thieno[3,2-d]pyrimidine 5,5-dioxides

    Directory of Open Access Journals (Sweden)

    Kenichirou Yokota

    2012-02-01

    Full Text Available New fluorescent compounds, benzo[4,5]thieno[3,2-d]pyrimidine 5,5-dioxides (3a–g, 2-amino-4-methylsulfanylbenzo[4,5]thieno[3,2-d]pyrimidine (6, and 2-amino-4-methylsulfanyl-7-methoxybenzo[4,5]furo[3,2-d]pyrimidine (7, were synthesized in good yields from heterocyclic ketene dithioacetals (1a–c and guanidine carbonate (2a or (S-methylisothiourea sulfate (2b in pyridine under reflux. Among the fused pyrimidine derivatives, compound 3c, which has an amino group at the 2-position and a benzylamino group at the 4-position of the pyrimidine ring, showed the strongest solid-state fluorescence. The absorption and emission properties of the compounds were quantitatively reproduced by a series of ab initio quantum-chemical calculations.

  18. Antagonists of the human A(2A) receptor. Part 6: Further optimization of pyrimidine-4-carboxamides.

    Science.gov (United States)

    Gillespie, Roger J; Bamford, Samantha J; Clay, Alex; Gaur, Suneel; Haymes, Tim; Jackson, Philip S; Jordan, Allan M; Klenke, Burkhard; Leonardi, Stefania; Liu, Jeanette; Mansell, Howard L; Ng, Sean; Saadi, Mona; Simmonite, Heather; Stratton, Gemma C; Todd, Richard S; Williamson, Douglas S; Yule, Ian A

    2009-09-15

    Antagonists of the human A(2A) receptor have been reported to have potential therapeutic benefit in the alleviation of the symptoms associated with neurodegenerative movement disorders such as Parkinson's disease. As part of our efforts to discover potent and selective antagonists of this receptor, we herein describe the detailed optimization and structure-activity relationships of a series of pyrimidine-4-carboxamides. These optimized derivatives display desirable physiochemical and pharmacokinetic profiles, which have led to promising oral activity in clinically relevant models of Parkinson's disease.

  19. Methylpalladium complexes with pyrimidine-functionalized N-heterocyclic carbene ligands

    Science.gov (United States)

    Meyer, Dirk

    2016-01-01

    Summary A series of methylpalladium(II) complexes with pyrimidine-NHC ligands carrying different aryl- and alkyl substituents R ([((pym)^(NHC-R))PdII(CH3)X] with X = Cl, CF3COO, CH3) has been prepared by transmetalation reactions from the corresponding silver complexes and chloro(methyl)(cyclooctadiene)palladium(II). The dimethyl(1-(2-pyrimidyl)-3-(2,6-diisopropylphenyl)imidazolin-2-ylidene)palladium(II) complex was synthesized via the free carbene route. All complexes were fully characterized by standard methods and in three cases also by a solid state structure. PMID:27559406

  20. Synthesis, in vitro antimicrobial and cytotoxic activities of novel pyrimidine-benzimidazol combinations.

    Science.gov (United States)

    Chen, Peng-Ju; Yang, Ang; Gu, Yi-Fei; Zhang, Xiao-Song; Shao, Kun-Peng; Xue, Deng-Qi; He, Peng; Jiang, Teng-Fei; Zhang, Qiu-Rong; Liu, Hong-Min

    2014-06-15

    A series of novel 4-substituted-2-{[(1H-benzo[d]imidazol-2-yl)methyl] thio}-6-methylpyrimidine derivatives were designed, synthesized and evaluated for their cytotoxic activities against four human cancer cell lines and inhibitory activities against five type culture strains in vitro. Some of synthetic pyrimidine-benzimidazol combinations showed good inhibitory activities against Stenotrophomonas maltophilia, especially compounds 7b and 7c. Compounds 7a and 7d exhibited enhanced activities against MGC-803 in vitro, when compared to 5-Fu.

  1. Polymerization in Liquid Crystal Medium: Preparation of Polythiophene Derivatives Bearing a Bulky Pyrimidine Substituent

    Directory of Open Access Journals (Sweden)

    Hiromasa Goto

    2010-10-01

    Full Text Available We carried out polycondensation of monomers bearing a bulky pyrimidine substituent in a liquid crystal solvent. The resultant polymers formed nematic liquid crystals. The polymers prepared in liquid crystals had higher coplanarity than the polymers prepared in toluene. This can be due to the fact that the ordered medium of the liquid crystal produces an aggregated structure with well-developed π-stacking between the main chains. The present results demonstrated that polymerization of bulky monomers is possible in liquid crystal solvents.

  2. [Quantum-chemical investigation of the elementary molecular mechanisms of pyrimidine-purine transversions].

    Science.gov (United States)

    Brovarets', O O; Govorun D M

    2010-01-01

    Purine-purine mispairs of DNA (thus involving template base in anti-conformation along the glycosidic bond and base of the incoming nucleotide - in syn-conformation) leading to pyrimidine-purine "transversions"-type point mutations were revealed and characterized at the MP2/6-311++G(2df,pd)//B3LYP/6-311++G(d,p) level of theory in vacuum approach adequately modeling hydrophobic environment of the active centre of high-fidelity replicative DNA-polymerases.

  3. Efficient and Selective Construction of Pyrrolo[3,2-d]pyrimidine Derivatives

    Energy Technology Data Exchange (ETDEWEB)

    He, Ping; Wu, Jing; Hu, Yanggen; Li, Zaifang; Hou, Qiufei; Wang, Yanling; Zhao, Kun; Zhang, Erli [Hubei Univ. of Arts and Science, Xiangyang (China)

    2014-02-15

    An efficient and selective method for the synthesis of ethyl 2-amino/aryloxy-3-aryl-4-oxo-5-phenyl-4,5-dihydro-3H-pyrrolo[3,2-d] pyrimidine-7-carboxylate derivatives has been developed. The main process involved the reaction of diethyl 1-phenyl-3-((triphenylphosphoranylidene)amino)-1H-pyrrole-2,4-dicarboxylate and aromatic isocyanates, followed by addition of amines/phenols in the presence of catalytic amount of sodium ethoxide or solid potassium carbonate.

  4. An Efficient Microwave-assisted Synthesis of Pyrido[2,3-d]pyrimidine Derivatives

    Institute of Scientific and Technical Information of China (English)

    TU Shujiang; WU Shanshan; HAN Zhengguo; HAO Wenjuan

    2009-01-01

    A series of new pyrido[2,3-d]pyrimidine derivatives were synthesized by multi-component reactions of equi-molar amount of aromatic aldehydes with barbituric acids (barbituric acid or 1,3-dimethylbarbituric acid) and 5-amino-2-methylbenzo[d]thiazol in mixed solvent of glacial acetic acid and ethylene glycol without catalyst under microwave irradiation. This one-pot method has the advantage of good yields (90%-93%), simple workup proce-dure and short reaction time (5 min).

  5. A convenient four-component one-pot strategy toward the synthesis of pyrazolo[3,4-d]pyrimidines

    Directory of Open Access Journals (Sweden)

    Mingxing Liu

    2015-11-01

    Full Text Available An efficient one-pot synthesis of pyrazolo[3,4-d]pyrimidine derivatives by the four-component condensation of hydrazines, methylenemalononitriles, aldehydes and alcohols has been developed via two different reaction pathways. The structures of target products were characterized by IR spectroscopy, NMR (1H and 13C spectroscopy and HRMS (ESI spectrometry. The crystal structure of 4-ethoxy-6-(2-nitrophenyl-1-phenyl-1H-pyrazolo[3,4-d]pyrimidine was determined by single crystal X-ray diffraction.

  6. From Label to Practice

    DEFF Research Database (Denmark)

    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...... actors and institutions to develop practices associated with the NNC label. Third, organized dissemination allowed the excitement and engagement with the new label to spread quickly....

  7. Capacitive label reader

    Science.gov (United States)

    Arlowe, H. Duane

    1985-01-01

    A capacitive label reader includes an outer ring transmitting portion, an inner ring transmitting portion, and a plurality of insulated receiving portions. A label is the mirror-image of the reader except that identifying portions corresponding to the receiving portions are insulated from only one of two coupling elements. Positive and negative pulses applied, respectively, to the two transmitting rings biased a CMOS shift register positively to either a 1 or 0 condition. The output of the CMOS may be read as an indication of the label.

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

    Institute of Scientific and Technical Information of China (English)

    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.

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

    Science.gov (United States)

    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.

  10. Purine and pyrimidine nucleosides preserve human astrocytoma cell adenylate energy charge under ischemic conditions.

    Science.gov (United States)

    Balestri, Francesco; Giannecchini, Michela; Sgarrella, Francesco; Carta, Maria Caterina; Tozzi, Maria Grazia; Camici, Marcella

    2007-02-01

    The brain depends on both glycolysis and mitochondrial oxidative phosphorylation for maintenance of ATP pools. Astrocytes play an integral role in brain functions providing trophic supports and energy substrates for neurons. In this paper, we report that human astrocytoma cells (ADF) undergoing ischemic conditions may use both purine and pyrimidine nucleosides as energy source to slow down cellular damage. The cells are subjected to metabolic stress conditions by exclusion of glucose and incubation with oligomycin (an inhibitor of oxidative phosphorylation). This treatment brings about a depletion of the ATP pool, with a concomitant increase in the AMP levels, which results in a significant decrease of the adenylate energy charge. The presence of purine nucleosides in the culture medium preserves the adenylate energy charge, and improves cell viability. Besides purine nucleosides, also pyrimidine nucleosides, such as uridine and, to a lesser extent, cytidine, are able to preserve the ATP pool. The determination of lactate in the incubation medium indicates that nucleosides can preserve the ATP pool through anaerobic glycolysis, thus pointing to a relevant role of the phosphorolytic cleavage of the N-glycosidic bond of nucleosides which generates, without energy expense, the phosphorylated pentose, which through the pentose phosphate pathway and glycolysis can be converted to energetic intermediates also in the absence of oxygen. In fact, ADF cells possess both purine nucleoside phosphorylase and uridine phosphorylase activities.

  11. OCLI-023, a Novel Pyrimidine Compound, Suppresses Osteoclastogenesis In Vitro and Alveolar Bone Resorption In Vivo

    Science.gov (United States)

    Kim, Ju Ang; Lee, Doohyun; Kim, Nam Doo; Shin, Hong-In; Bae, Yong Chul; Park, Eui Kyun

    2017-01-01

    An abnormal increase in osteoclast differentiation and activation results in various bone-resorptive diseases, including periodontitis, rheumatoid arthritis, and osteoporosis. Chemical compounds containing pyrimidine ring have been shown to regulate a variety of biological processes. Therefore, in order to identify an antiresorptive agent, we synthesized a series of pyrimidine ring-containing chemical compounds, and found that OCLI-023 suppressed the differentiation and activation of osteoclasts in vitro. OCLI-023 directly inhibited receptor activator of nuclear factor-κB ligand (RANKL)-induced differentiation of bone marrow macrophages into osteoclasts, without a cytotoxic response. OCLI-023 also downregulated the RANKL-induced mRNA expression of osteoclast markers as well as inhibited the formation of actin rings and resorption pits. OCLI-023 attenuated the RANKL-induced activation of c-Jun N-terminal kinase and nuclear factor kappa-light-chain-enhancer of activated B cell signaling pathways. In a mouse model of periodontitis, ligature induced an increase of distance between cementoenamel junction (CEJ) and alveolar bone crest (ABC) in the second molar, and OCLI-023 significantly reduced it. Histological analysis showed ligature-induced increase of osteoclast numbers was also significantly reduced by OCLI-023. These data demonstrated the inhibitory effect of OCLI-023 on osteoclast differentiation and activity of osteoclasts in vitro, as well as on ligature-induced bone loss in vivo, and OCLI-023 can be proposed as a novel anti-resorptive compound. PMID:28085946

  12. Synthesis and evaluation of a classical 2,4-diamino-5-substituted-furo[2,3-d]pyrimidine and a 2-amino-4-oxo-6-substituted-pyrrolo[2,3-d]pyrimidine as antifolates☆

    Science.gov (United States)

    Gangjee, Aleem; Yang, Jie; McGuire, John J.; Kisliuk, Roy L.

    2013-01-01

    Two classical antifolates, a 2,4-diamino-5-substituted furo[2,3-d]pyrimidine and a 2-amino-4-oxo-6-substituted pyrrolo[2,3-d]pyrimidine, were synthesized as potential inhibitors of dihydrofolate reductase (DHFR) and thymidylate synthase (TS). The syntheses were accomplished by condensation of 2,6-diamino-3(H)-4-oxo-pyrimidine with α-chloro-ketone 21 to afford two key intermediates 23 and 24, followed by hydrolysis, coupling with l-glutamate diethyl ester and saponification of the diethyl ester to afford the classical antifolates 13 and 14. Compounds 13 and 14 with a single carbon atom bridge are both substrates for folylpoly-γ-glutamate synthetase (FPGS), the enzyme responsible for forming critical poly-γ-glutamate antifolate metabolites with increased potency and/or increased cell retention. Compound 14 is a highly efficient FPGS substrate demonstrating that 2,4-diamino-5-substituted furo[2,3-d]pyrimidines are important lead structures for the design of antifolates with FPGS substrate activity. It retains inhibitory potency for DHFR and TS compared to the two atom bridged analog 5. Compound 13 is a poor inhibitor of purified DHFR and TS, and both 13 and 14 are poor inhibitors of the growth of CCRF-CEM human leukemia cells in culture, indicating that single carbon bridged compounds in these series though conducive to FPGS substrate activity were not potent inhibitors. PMID:16990006

  13. Food Label and You

    Medline Plus

    Full Text Available ... Sports show highlighting the importance of using the nutrition facts label to control portions, fat, calories and percent daily value. Two studio "sports announcers" describe the "game day" food action of ...

  14. FDA Online Label Repository

    Data.gov (United States)

    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 Drug...

  15. Figuring Out Food Labels

    Science.gov (United States)

    ... usually appears on the back or side of packaging under the title "Nutrition Facts." It's also displayed in grocery stores near fresh foods, like fruits, vegetables, and fish. The nutrition facts label includes: a column of ...

  16. Food Label and You

    Medline Plus

    Full Text Available ... use the Nutrition Facts Label to make informed food choices. You can view the new video in its ... two sites, comparing serving sizes, ingredients and overall food choices in this "Battle of the Dueling Dinner Parties". ...

  17. Behind the Label "Alcoholic."

    Science.gov (United States)

    Wright, Deborah M.

    1989-01-01

    Relates individual's personal story of her childhood influenced by her parent's alcoholism, her own alcoholism as a young adult, and her experiences with counseling. Asks others not to reject her because of the label "alcoholic." (ABL)

  18. Food Label and You

    Medline Plus

    Full Text Available ... main page content Skip to search Skip to topics menu Skip to common links HHS U.S. Department ... a contestant in food label knowledge. Questions cover topics such as Calories, Serving Size, Servings per Container, ...

  19. Elucidating the mechanism of cytochrome P450-mediated pyrimidine ring conversion to pyrazole metabolites with the BACE1 inhibitor GNE-892 in rats.

    Science.gov (United States)

    Takahashi, Ryan; Ma, Shuguang; Deese, Alan; Yue, Qin; Kim-Kang, Heasook; Yi, Yijun; Siu, Michael; Hunt, Kevin W; Kallan, Nicholas C; Hop, Cornelis E C A; Liu, Xingrong; Khojasteh, S Cyrus

    2014-05-01

    We investigated an uncommon biotransformation of pyrimidine during the metabolism of GNE-892 ((R)-2-amino-1,3',3'-trimethyl-7'-(pyrimidin-5-yl)-3',4'-dihydro-2'H-spiro[imidazole-4,1'-naphthalen]-5(1H)-one), a β-secretase 1 inhibitor. Three novel metabolites, formed by conversion of pyrimidine to pyrazole, were observed in the (14)C-radiolabeled mass balance study in rats. Their structures were characterized by high-resolution mass spectrometry and nuclear magnetic resonance. Although these metabolites accounted for pyrazole-containing metabolites were formed in vitro with rat hepatocytes and liver microsomes, which supported that they were formed during hepatic metabolism. Further, their generation was inhibited by 1-aminobenzotriazole, indicating involvement of cytochrome P450s. Studies with rat recombinant enzymes identified that CYP2D2 generated the N-hydroxypyrazole metabolite from GNE-892. This biotransformation proceeded through multiple steps from the likely precursor, pyrimidine N-oxide. On the basis of these data, we propose a mechanism in which the pyrimidine is activated via N-oxidation, followed by a second oxidative process that opens the pyrimidine ring to form a formamide intermediate. After hydrolysis of the formamide, a carbon is lost as formic acid, together with ring closure to form the pyrazole ring. This article highlights a mechanistic approach for determining the biotransformation of the pyrimidine to a pyrazole for GNE-892.

  20. [Effect of hydroxylated pyrimidine derivatives on activities of thiamine-dependent enzymes and some parameters of lipid metabolism in mice].

    Science.gov (United States)

    Oparin, D A; Gorenshteĭn, B I; Karaedova, L M; Naruta, E E; Zabrodskaia, S V; Rudiak, T V; Akat'ev, V E; Larin, F S

    1997-01-01

    It has been found that hydroxylated pyrimidine derivatives actively participate in metabolic proceeds related to functioning of vitamin B1-dependent enzymes (transketolase, 2-oxo acid dehydrogenase). Hydroxypyrimidines also induce a significant increase in the levels of total lipids and cholesterol in the mice liver, not changing the phospholipid content.

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

    DEFF Research Database (Denmark)

    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 rat...

  2. Synthesis, structural, conformational and DFT studies of N-3 and O-4 alkylated regioisomers of 5-(hydroxypropyl)pyrimidine

    Science.gov (United States)

    Salihović, Mirsada; Osmanović, Amar; Špirtović-Halilović, Selma; Roca, Sunčica; Meščić, Andrijana; Vujisić, Ljubodrag; Trifunović, Snežana; Završnik, Davorka; Sofić, Emin

    2015-07-01

    Because of the great pharmacological potential of the pyrimidine motif, novel C-5 substituted N-3 acyclic and O-4 acyclic pyrimidine derivatives were prepared as an interesting class of compounds for biological evaluation. Introduction of the 2,3-dihydroxypropyl (DHP) and penciclovir (PCV)-like side chains to 2-methoxypyrimidin-4-one (2) afforded a mixture of N- and O-acyclic pyrimidine nucleosides in the ratio of 54: 29 (3:4) and 57:21 (5:6) with N-3 isomer being dominant. Distinction between N- and O-alkylated pyrimidine moiety was deduced from extensive experimental FT-IR, HPLC-MS and 1D (1H, 13C) and 2D (COSY, HMQC and HMBC) NMR analyses. The N-, O-regioisomers were also examined by computational method at density functional theory (DFT) RB3LYP/6-31G(d), 6-31G∗∗ and 6-31+G∗ levels. DFT global chemical reactivity descriptors (total energy, chemical hardness, electronic chemical potential and electrophilicity) were calculated for the isomers and used to predict and describe their relative stability and reactivity. The chemical reactivity indices were related to the C2sbnd N3sbnd C4 bond angle. Theoretical predictions can be used to compare chemical reactivity and stability with future biological evaluation and behaviour of these compounds.

  3. A microenvironment-sensitive fluorescent pyrimidine ribonucleoside analogue: synthesis, enzymatic incorporation, and fluorescence detection of a DNA abasic site.

    Science.gov (United States)

    Tanpure, Arun A; Srivatsan, Seergazhi G

    2011-11-04

    Base-modified fluorescent ribonucleoside-analogue probes are valuable tools in monitoring RNA structure and function because they closely resemble the structure of natural nucleobases. Especially, 2-aminopurine, a highly environment-sensitive adenosine analogue, is the most extensively utilized fluorescent nucleoside analogue. However, only a few isosteric pyrimidine ribonucleoside analogues that are suitable for probing the structure and recognition properties of RNA molecules are available. Herein, we describe the synthesis and photophysical characterization of a small series of base-modified pyrimidine ribonucleoside analogues derived from tagging indole, N-methylindole, and benzofuran onto the 5-position of uracil. One of the analogues, based on a 5-(benzofuran-2-yl)pyrimidine core, shows emission in the visible region with a reasonable quantum yield and, importantly, displays excellent solvatochromism. The corresponding triphosphate substrate is effectively incorporated into oligoribonucleotides by T7 RNA polymerase to produce fluorescent oligoribonucleotide constructs. Steady-state and time-resolved spectroscopic studies with fluorescent oligoribonucleotide constructs demonstrate that the fluorescent ribonucleoside photophysically responds to subtle changes in its environment brought about by the interaction of the chromophore with neighboring bases. In particular, the emissive ribonucleoside, if incorporated into an oligoribonucleotide, positively reports the presence of a DNA abasic site with an appreciable enhancement in fluorescence intensity. The straightforward synthesis, amicability to enzymatic incorporation, and sensitivity to changes in the microenvironment highlight the potential of the benzofuran-conjugated pyrimidine ribonucleoside as an efficient fluorescent probe to investigate nucleic acid structure, dynamics, and recognition events.

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

    DEFF Research Database (Denmark)

    Thomsen, Anne Engelbrecht; Friedrichsen, Gerda Marie; Sørensen, Arne Hagsten

    2003-01-01

    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...

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

  6. Ethyl 2-(5-fluoro-3-methylsulfinyl-1-benzofuran-2-ylacetate

    Directory of Open Access Journals (Sweden)

    Hong Dae Choi

    2009-08-01

    Full Text Available In the title compound, C13H13FO4S, the O atom and the methyl group of the methylsulfinyl substituent lie on opposite sides of the plane through the benzofuran fragment. The crystal structure exhibits four intermolecular non-classical C—H...O hydrogen bonds. In addition, the crystal structure contains aromatic π–π interactions between the furan and benzene rings of adjacent molecules [centroid–centroid distance = 3.743 (2 Å], and two intermolecular C—H...π interactions.

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

    Directory of Open Access Journals (Sweden)

    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.

  8. CCDC 1436716: Experimental Crystal Structure Determination : 5-fluoro-4-iodo-2,1,3-benzothiadiazole

    KAUST Repository

    Shi, Qinqin

    2016-01-01

    An entry from the Cambridge Structural Database, the world’s repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, cell parameters, space group, experimental conditions and quality measures.

  9. 5-Fluoro-N′-[(E-4-methoxybenzylidene]-3-phenyl-1H-indole-2-carbohydrazide

    Directory of Open Access Journals (Sweden)

    Mehmet Akkurt

    2010-04-01

    Full Text Available In the title molecule, C23H18FN3O2, the mean plane of the indole system forms dihedral angles of 44.23 (8 and 14.54 (7°, respectively, with the phenyl and benzene rings. In the crystal, intermolecular N—H...O hydrogen bonds link molecules into two-layer ribbons extended along the b axis. The crystal packing also exhibits weak intermolecular C—H...O, C—H...F and C—H...π interactions.

  10. N′-(4-Ethylcyclohexylidene-5-fluoro-3-phenyl-1H-indole-2-carbohydrazide

    Directory of Open Access Journals (Sweden)

    Orhan Büyükgüngör

    2013-08-01

    Full Text Available The title compound, C23H24FN3O, crystallizes with two independent molecules (I and II in the asymmetric unit. These pairs of molecules are linked to each other as N—H...O dimers with an R22(10 motif. Furthermore, the crystal structure also exhibits C—H...π interactions. The atoms of the ethyl group in molecule I are disordered over two sites with an occupancy ratio of 0.817 (6:0.183 (6.

  11. 5-Fluoro-3-phenyl-N′-(4-propylcyclohexylidene-1H-indole-2-carbohydrazide

    Directory of Open Access Journals (Sweden)

    Orhan Büyükgüngör

    2013-08-01

    Full Text Available In the title compound, C24H26FN3O, the cyclohexane ring adopts a chair conformation; the propyl substituent is in an equatorial orientation and the bond-angle sum at the C atom bonded to the carbohydrazide N atom is 360.0°. The dihedral angle between the 1H-indole ring system and the phenyl ring is 82.77 (13°. A weak intramolecular C—H...π contact occurs. In the crystal, pairs of molecules related by a crystallographic twofold axis are linked by bifurcated N—H...(O,N hydrogen bonds; a C—H...O interaction occurs between the same pair. The dimers are linked by C—H...F and C—H...π interactions, generating a three-dimensional network.

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

    Indian Academy of Sciences (India)

    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.

  13. Supramolecular systems based on novel mono- and dicationic pyrimidinic amphiphiles and oligonucleotides: a self-organization and complexation study.

    Science.gov (United States)

    Zakharova, Lucia; Voronin, Mikhail; Semenov, Vyacheslav; Gabdrakhmanov, Dinar; Syakaev, Victor; Gogolev, Yuri; Giniyatullin, Rashit; Lukashenko, Svetlana; Reznik, Vladimir; Latypov, Shamil; Konovalov, Alexander; Zuev, Yuri

    2012-02-01

    Novel mono- and dicationic pyrimidinic surfactants are synthesized and their aggregation behavior is studied by methods of tensiometry and nuclear magnetic resonance (NMR) self-diffusion. To estimate their potentiality as gene delivery agents, the complexation with oligonucleotides (ONus) is explored by dynamic light scattering (DLS) and zeta-potential titration methods and ethidium bromide exclusion experiments. Bola-type pyrimidinic amphiphile (BPM) demonstrates rather a weak affinity to ONus. Although it induces mixed associations with ONus, only slight charge compensation changes occur at a large excess of bola, with no recharging reached. Similarly, the ethydium bromide exclusion study reveals a slow increase in the binding capacity toward an ONu with an increment in BPM concentration. The monocationic pyrimidinic surfactant (MPM) and its gemini analogue (GPM-1) are ranked as intermediates in both their aggregative activity and complexing properties toward ONus. They both form mixed associates with ONus well below the critical micelle concentrations (cmcs) of 2 and 15 mM respectively. However, GPM-1 has a much lower isoelectric point at the molar ratio surfactant/ONu r~1 compared to r~3 for MPM. This probably indicates a larger electrostatic contribution to the ONu complexation in the case of GPM-1. The most hydrophobic pyrimidinic surfactant (GPM-2), bearing three alkyl tails, demonstrates enhanced aggregative activity and binding capacity toward ONus as compared to former pyrimidinic surfactants. Due to effective aggregative (low cmc of 0.04 mM) plus binding properties (fraction of bound ONu β=0.76 at r=2.5), GPM-2 may be ranked as a promising agent for wider biological applications. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  14. European consumers and nutrition labelling

    DEFF Research Database (Denmark)

    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...

  15. Distance labeling schemes for trees

    DEFF Research Database (Denmark)

    Alstrup, Stephen; Gørtz, Inge Li; Bistrup Halvorsen, Esben;

    2016-01-01

    We consider distance labeling schemes for trees: given a tree with n nodes, label the nodes with binary strings such that, given the labels of any two nodes, one can determine, by looking only at the labels, the distance in the tree between the two nodes. A lower bound by Gavoille et al. [Gavoill...

  16. European consumers and nutrition labelling

    DEFF Research Database (Denmark)

    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...

  17. Distance labeling schemes for trees

    DEFF Research Database (Denmark)

    Alstrup, Stephen; Gørtz, Inge Li; Bistrup Halvorsen, Esben

    2016-01-01

    We consider distance labeling schemes for trees: given a tree with n nodes, label the nodes with binary strings such that, given the labels of any two nodes, one can determine, by looking only at the labels, the distance in the tree between the two nodes. A lower bound by Gavoille et al. [Gavoille...... variants such as, for example, small distances in trees [Alstrup et al., SODA, 2003]. We improve the known upper and lower bounds of exact distance labeling by showing that 1/4 log2(n) bits are needed and that 1/2 log2(n) bits are sufficient. We also give (1 + ε)-stretch labeling schemes using Theta......(log(n)) bits for constant ε> 0. (1 + ε)-stretch labeling schemes with polylogarithmic label size have previously been established for doubling dimension graphs by Talwar [Talwar, STOC, 2004]. In addition, we present matching upper and lower bounds for distance labeling for caterpillars, showing that labels...

  18. Synthesis and biological evaluation of novel pyrimidine-benzimidazol hybrids as potential anticancer agents.

    Science.gov (United States)

    Shao, Kun-Peng; Zhang, Xu-Yao; Chen, Peng-Ju; Xue, Deng-Qi; He, Peng; Ma, Li-Ying; Zheng, Jia-Xin; Zhang, Qiu-Rong; Liu, Hong-Min

    2014-08-15

    A series of pyrimidine-benzimidazol hybrids was synthesized and evaluated for anticancer activity on four human cancer cell lines including MCF-7, MGC-803, EC-9706 and SMMC-7721. Some of the synthesized compounds exhibited moderate to potent activity against MGC-803 and MCF-7. Among them, compounds 5a-b and 6a-b showed most effective activity. Compounds 5b and 6b were more cytotoxic than 5-fluorouracil against all tested four human cancer cell lines, with IC50 values ranging from 2.03 to 10.55 μM and 1.06 to 12.89 μM, respectively. Flow cytometry analysis demonstrated that treatment of MGC-803 with 6b led to cell cycle arrest at G2/M phase accompanied by an increase in apoptotic cell death.

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

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

    Indian Academy of Sciences (India)

    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.

  1. Syntheses and anti-microbial evaluation of new quinoline scaffold derived pyrimidine derivatives

    Directory of Open Access Journals (Sweden)

    Shikha S. Dave

    2016-09-01

    Full Text Available A series of diversely substituted chalcones derived from a quinoline scaffold, e.g. (E-3-(2-chloroquinolin-3-yl-1-(2-hydroxyphenyl prop-2-en-1-one and its pyrimidine analogues e.g. 2-[2-amino-6-(2-chloroquinolin-3-yl-5,6-dihydropyrimidin-4-yl]phenols have been prepared by condensation of 2-chloro-3-formyl quinoline with differently substituted 2-hydroxy acetophenones and further treatment with guanidine carbonate. All the newly synthesized compounds have been evaluated for their in vitro growth inhibitory activity against Escherichia coli, Pseudomonas vulgaris, Bacillus subtilis, Staphylococcus aureus, Staphylococcus typhi, Candida albicans, Aspergillus niger and Pseudomonas chrysogenum.

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Science.gov (United States)

    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.

  4. Synthesis of Polynuclear Heterocyclic Compounds Derived from Thieno[2,3-d]pyrimidine Derivatives

    Directory of Open Access Journals (Sweden)

    N. A. Hassan

    2000-06-01

    Full Text Available Reaction of 2-hydrazino-3-methyl-3,4-dihydrothieno[2,3-d]pyrimidin-4-one derivatives 2a,b with aliphatic acids afforded the thienotriazolopyrimidinone derivatives 3a-d, with nitrous acid yielded tetrazolothienopyrimidinone derivatives 4a,b and with carbon disulphide furnished 3-mercaptothienotriazolopyrimidinone derivatives 5a,b. Also, 2a,b reacted with aldehydes to afford the arylhydrazones 6a-f which cyclized into thienotriazolopyrimidinone derivatives 7a-f. Furthermore, 2a,b condensed with ethyl acetoacetate and ethyl cyanoacetate to afford 2-(1-pyrazolyl derivatives 9a,b and 10a,b, respectively. On the other hand, 2-hydrazino derivatives 2a,b condensed with a-halo-ketones to yield thienpyrimidotriazinone derivatives 11a,b and with β-diketones, to form 2-(1-pyrazolyl derivatives 12a-f.

  5. Crystal structure of the nucleosome containing ultraviolet light-induced cyclobutane pyrimidine dimer.

    Science.gov (United States)

    Horikoshi, Naoki; Tachiwana, Hiroaki; Kagawa, Wataru; Osakabe, Akihisa; Matsumoto, Syota; Iwai, Shigenori; Sugasawa, Kaoru; Kurumizaka, Hitoshi

    2016-02-26

    The cyclobutane pyrimidine dimer (CPD) is induced in genomic DNA by ultraviolet (UV) light. In mammals, this photolesion is primarily induced within nucleosomal DNA, and repaired exclusively by the nucleotide excision repair (NER) pathway. However, the mechanism by which the CPD is accommodated within the nucleosome has remained unknown. We now report the crystal structure of a nucleosome containing CPDs. In the nucleosome, the CPD induces only limited local backbone distortion, and the affected bases are accommodated within the duplex. Interestingly, one of the affected thymine bases is located within 3.0 Å from the undamaged complementary adenine base, suggesting the formation of complementary hydrogen bonds in the nucleosome. We also found that UV-DDB, which binds the CPD at the initial stage of the NER pathway, also efficiently binds to the nucleosomal CPD. These results provide important structural and biochemical information for understanding how the CPD is accommodated and recognized in chromatin.

  6. An efficient one-pot synthesis, characterization and antibacterial activity of novel chromeno-pyrimidine derivatives

    Science.gov (United States)

    Suresh, Lingala; Kumar, P. Sagar Vijay; Chandramouli, G. V. P.

    2017-04-01

    A simple and efficient one-pot three component, green protocol was established for the synthesis of chromenopyrano[2,3-d]pyrimidine derivatives starting from 3-amino-pyrano[2,3-c]chromene-2-carbonitrile, N,N-dimethylformamide dimethylacetal and aromatic amines in the presence of 1-butyl-3-methylimidazolium hydrogen sulphate[Bmim]HSO4 ionic liquid. The present procedure offers a domino reaction strategy, cleaner conversion, short reaction times and high yields. Among the screened derivatives, the compounds 4g and 4h were identified as lead molecules which established promising antimicrobial towards Gram-positive bacterial strains such as Staphylococcus aureus MTCC 96, Staphylococcus aureus MLS16 MTCC 2940 and Bacillus subtilis MTCC 121.

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

  8. Novel pyrazole-5-carboxamide and pyrazole-pyrimidine derivatives: synthesis and anticancer activity.

    Science.gov (United States)

    Shi, Jing Bo; Tang, Wen Jian; Qi, Xing Bao; Li, Rong; Liu, Xin Hua

    2015-01-27

    A series of novel pyrazole-5-carboxamide and pyrazole-pyrimidine derivatives were designed and synthesized. All compounds have been screened for their antiproliferative activity against MGC-803, SGC-7901 and Bcap-37 cell lines in vitro. The results revealed that compounds 8a, 8c and 8e exhibited strong inhibitory activity against MGC-803 cell line. The flow cytometric analysis result showed that compound 8e could inhibit MGC-803 proliferation. Some title compounds were tested against telomerase, and compound 8e showed the most potent inhibitory activity with IC50 value at 1.02 ± 0.08 μM. The docking simulation of compound 8e was performed to get the probable binding model, among them, LYS 189, LYS 372, LYS 249 and ASP 254 may be the key residues for the telomerase activity.

  9. Semantic Role Labeling

    CERN Document Server

    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

  10. Labeling of Patient Specimens

    Science.gov (United States)

    2011-01-26

    noted during the event that the actu.al number of near miss incidmts reported monthly was low due to laboratory personnel performing rounds each...specimens never leaves label and if moved it is labeled), All orders in system and all near misses and errors reported to patient safety Purchase/Install...Meeting 14 Aug 09, 1400 in lab break room thru out Develop TICK sheet to track near misses .JDI Ms. Clark Clinics will provide toPS 1st working day of

  11. Trifunctional fluorescent unnatural nucleoside: Label free detection of T-T/C-C base mismatches, abasic site and bulge DNA.

    Science.gov (United States)

    Bag, Subhendu Sekhar; Pradhan, Manoj Kumar; Talukdar, Sangita

    2017-08-01

    The detection and targeting of both the mismatched and abasic DNA is highly important which would ultimately help in designing new diagnostics and chemotherapeutics. Furthermore, sensing and targeting the bulge sequence with a fluorescent probe would be useful to study the role of bulges in nucleic acid function or could have significant therapeutic potential. Thus, detection of specific bulges by small fluorescent molecules is an attractive research area since the past several years. Many attempts have been made to prepare such compounds. We report herein a label free strategy for the detection of pyrimidine base mismatches (T/T and C/C), sensing of abasic site, and pyrimidine base bulge DNA using an unnatural tetrazolylpyrene nucleoside ((TPy)B(Do)) as a bare fluorescent probe. The H-bonding/hydrophobic force mediated interactions allow the sensing of all three deformed DNA via an enhancement of fluorescence signal using our simple "Just-Mix and Read" strategy. The binding of the probe to all the three deformed DNA duplexes is accompanied by an increase in the thermal melting stability of the deformed DNAs. That the probe binds efficiently to the minor groove near the deformed site was evident from spectroscopic studies. All the spectral evidences open up a multitude of possibilities for using our probe, tetrazolylpyrene nucleoside, as an efficient fluorescent light-up bio-probe for label free DNA detection. Copyright © 2017. Published by Elsevier B.V.

  12. Design, synthesis and vasorelaxant evaluation of novel coumarin-pyrimidine hybrids.

    Science.gov (United States)

    Amin, Kamilia M; Awadalla, Fadi M; Eissa, Amal A M; Abou-Seri, Sahar M; Hassan, Ghaneya S

    2011-10-15

    The main objective of the present work depends on the hybridization of coumarin moiety as a vasorelaxant scaffold and pyrimidine ring with known potential cardiovascular activity in order to prepare some new potent antihypertensive candidates. Hence, two groups of pyrimidinyl coumarin derivatives were synthesized and evaluated for their vasorelaxing activity. These compounds were prepared via two routes; either preparation of the guanidinocoumarin 4 followed by a cocktail of cyclization reactions to yield a different array of 6-(substituted pyrimidin-2-yl)aminocoumarins 5-17, or through cyclization of the precursor chalcones 22a-g with guanidine hydrochloride to generate the corresponding final compounds, 8-(6-aryl-2-aminopyrimidin-4-yl)-7-methoxycoumarins 23a-g. The effect of these compounds and the coumarin intermediates 3, 4, 21 and 22a-g on nor-epinephrine induced contracture in thoracic rat aortic rings was investigated using prazocin as reference drug. Several derivatives showed promising activities either equal or even better than that of prazocin (IC(50) 0.487 mM). The most prospective compounds; the pyrimidinylamino coumarin derivatives 8, 17 (IC(50) 0.411, IC(50) 0.421 mM) and the chalcones 22b, 22e (IC(50) 0.371, 0.374 mM) that displayed the highest activity can be a base for lead optimization and simple but efficient design of new compounds. 2D-QSAR analysis was applied to find a correlation between the experimental vasorelaxant activities of the newly synthesized coumarin derivatives and their different physicochemical parameters. The result of this study showed that the increase in aqueous solubility while retaining good hydrophobic character of the overall molecule is the key for maintaining high relaxation activity.

  13. UVA-induced cyclobutane pyrimidine dimers in DNA: a direct photochemical mechanism?

    Science.gov (United States)

    Mouret, Stéphane; Philippe, Coralie; Gracia-Chantegrel, Jocelyne; Banyasz, Akos; Karpati, Szilvia; Markovitsi, Dimitra; Douki, Thierry

    2010-04-07

    The carcinogenic action of UVA radiation is commonly attributed to DNA oxidation mediated by endogenous photosensitisers. Yet, it was recently shown that cyclobutane pyrimidine dimers (CPD), well known for their involvement in UVB genotoxicity, are produced in larger yield than oxidative lesions in UVA-irradiated cells and skin. In the present work, we gathered mechanistic information on this photoreaction by comparing formation of all possible bipyrimidine photoproducts upon UVA irradiation of cells, purified genomic DNA and dA(20):dT(20) oligonucleotide duplex. We observed that the distribution of photoproducts, characterized by the sole formation of CPD and the absence of (6-4) photoproducts was similar in the three types of samples. The CPD involving two thymines represented 90% of the amount of photoproducts. Moreover, the yields of formation of the DNA lesions were similar in cells and isolated DNA. In addition, the effect of the wavelength of the incident photons was found to be the same in isolated DNA and cells. This set of data shows that UVA-induced cyclobutane pyrimidine dimers are formed via a direct photochemical mechanism, without mediation of a cellular photosensitiser. This is possible because the double-stranded structure increases the capacity of DNA bases to absorb UVA photons, as evidenced in the case of the oligomer dA(20):dT(20). These results emphasize the need to consider UVA in the carcinogenic effects of sunlight. An efficient photoprotection is needed that can only be complete by completely blocking incident photons, rather than by systemic approaches such as antioxidant supplementation.

  14. Synthesis of some pyrazolines and pyrimidines derived from polymethoxy chalcones as anticancer and antimicrobial agents.

    Science.gov (United States)

    Rostom, Sherif A F; Badr, Mona H; Abd El Razik, Heba A; Ashour, Hayam M A; Abdel Wahab, Abeer E

    2011-09-01

    The synthesis of a series of certain polymethoxy chalcones and some derived pyrazole, pyrimidine, and thiazolopyrimidine ring structures is reported. Eleven compounds 4, 6, 9, 11, 14-17, 22, 24, and 25 were selected by the National Cancer Institute (NCI) to be screened for their in-vitro anticancer activity, whereas all the synthesized compounds were evaluated for their in-vitro antimicrobial activity. Compounds 4, 6, and 11 were found to possess a significant broad spectrum antitumor potential against most of the tested subpanel tumor cell lines. The pyrazolines 4 and 6 displayed remarkable growth inhibitory activities (GI(50) MG-MID values of 2.10 and 1.38 µM, respectively), together with moderate cytostatic effects (TGI MG-MID values of 47.9 and 42.7 µM, respectively). Meanwhile, the pyrimidin-2-one 11 showed a noticeable overall tumor growth inhibitory activity, together with high cytostatic and cytotoxic efficacies (GI(50) , TGI and LC(50) MG-MID values of 3.39, 17.4, and 61.7 µM, respectively). On the other hand, compounds 3, 4, 13, 15, 19, 20, and 23 were found to be the most active antimicrobial members in this investigation with a broad spectrum of activity. Compound 23 was four times superior to ampicillin against Pseudomonas aeruginosa. The best antifungal activity was demonstrated by compounds 4, 5, and 11 which possessed almost half the activity of clotrimazole against Candida albicans. Collectively, the obtained biological results suggest that compound 4 could be considered as a possible dual antimicrobial-anticancer agent.

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Indian Academy of Sciences (India)

    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.

  17. Synthesis of New Bis-Alkylated Phosphono Alkenyl Acyclonucleosides : (Z) and (E)-Diethyl-2-(3-alkyl pyrimidin-1-yl)ethylen-1-yl Phosphonate

    OpenAIRE

    Imbach, J L; J. L. Barascut; Lazrek, H B; Taourirte, M.; Rochdi, A.

    2000-01-01

    The E- and Z- phosphonoalkenyl acyclonucleosides of uracil and thymine were synthesized under Michael addition conditions. Introduction of an alkyl, alkenyl or alkynyl group at the N-3 position of the pyrimidine moiety was accomplished using potassium carbonate in DMF.

  18. Labelled Execution Systems

    Science.gov (United States)

    2012-05-07

    This is most starkly evident in the classical example used to demonstrate that, in the case of infinitely branching systems, a transfinite number of... transfinite number of iterations to converge, what can be shown to fail by appropriately embedding the labelled transition systems of [46, prop. 10.5

  19. Waisda?: video labeling game

    NARCIS (Netherlands)

    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

  20. Multi-label

    Directory of Open Access Journals (Sweden)

    Neda Abdelhamid

    2015-01-01

    Full Text Available Generating multi-label rules in associative classification (AC from single label data sets is considered a challenging task making the number of existing algorithms for this task rare. Current AC algorithms produce only the largest frequency class connected with a rule in the training data set and discard all other classes even though these classes have data representation with the rule’s body. In this paper, we deal with the above problem by proposing an AC algorithm called Enhanced Multi-label Classifiers based Associative Classification (eMCAC. This algorithm discovers rules associated with a set of classes from single label data that other current AC algorithms are unable to induce. Furthermore, eMCAC minimises the number of extracted rules using a classifier building method. The proposed algorithm has been tested on a real world application data set related to website phishing and the results reveal that eMCAC’s accuracy is highly competitive if contrasted with other known AC and classic classification algorithms in data mining. Lastly, the experimental results show that our algorithm is able to derive new rules from the phishing data sets that end-users can exploit in decision making.

  1. Food Label and You

    Medline Plus

    Full Text Available ... Label and You — Video Share Tweet Linkedin Pin it More sharing options Linkedin Pin it Email Print NOTE: FDA has issued final changes ... choices. You can view the new video in its entirety or select on any of the individual ...

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

    Energy Technology Data Exchange (ETDEWEB)

    Likar, Yury; Dobrenkov, Konstantin; Olszewska, Malgorzata; Shenker, Larissa; Hricak, Hedvig; Ponomarev, Vladimir [Memorial Sloan-Kettering Cancer Center, Molecular Imaging Laboratory, Department of Radiology, New York, NY (United States); Cai, Shangde [Memorial Sloan-Kettering Cancer Center, Radiochemistry/Cyclotron Core Facility, New York, NY (United States)

    2009-08-15

    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 {sup 3}H-FEAU pyrimidine nucleoside and low {sup 3}H-penciclovir acycloguanosine analog uptake in vitro. PET imaging also demonstrated high {sup 18}F-FEAU and low {sup 18}F-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 {sup 18}F-FEAU and an acycloguanosine-based {sup 18}F-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.)

  3. Design, Synthesis and Biological Evaluation of Novel Pyrimido[4,5-d]pyrimidine CDK2 Inhibitors as Anti-Tumor Agents

    Science.gov (United States)

    El-Moghazy, Samir M.; Ibrahim, Diaa A.; Abdelgawad, Nagwa M.; Farag, Nahla A. H.; El-Khouly, Ahmad S.

    2011-01-01

    A series of 2,5,7-trisubstituted pyrimido[4,5-d]pyrimidine cyclin-dependent kinase (CDK2) inhibitors is designed and synthesized. 6-Amino-2-thiouracil is reacted with an aldehyde and thiourea to prepare the pyrimido[4,5-d]-pyrimidines. Alkylation and amination of the latter ones give different amino derivatives. These compounds show potent and selective CDK inhibitory activities and inhibit in vitro cellular proliferation in cultured human tumor cells. PMID:21886895

  4. Health Labeling, and Consumption- Understanding Determinants To Health Label Use.

    OpenAIRE

    Hoyer, David; Dossing, Jens; Zhuravleva, Anna

    2013-01-01

    Consumer behavior was explored through the understanding, and use of health labeling. Government and business forces were discovered to influence the ability of consumers to use health labels for improved health and life expectancy, and reduce the negative health care costs of food related diseases. Our survey results were compared to other papers and experiments in the field of consumption and labeling. We discovered high usage of labels, especially nutrition information, and a desire for fr...

  5. Bis{μ-2-[(pyrimidin-2-yl)amino-meth-yl]phenolato}-κ(2) N (1):O;κ(2) O:N (1)-bis-({2-[(pyrimidin-2-yl-κN)amino-meth-yl]phenol}silver(I)) dihydrate.

    Science.gov (United States)

    Gao, Shan; Ng, Seik Weng

    2012-12-01

    The Ag(I) atom in the title centrosymmetric dinuclear compound, [Ag2(C11H10N3O)2(C11H11N3O)2]·2H2O, shows a T-shaped coordination arising from bonding to the N atom of a neutral 2-[(pyrimidin-2-yl)amino-meth-yl]phenol ligand, the N atom of the 2-[(pyrimidin-2-yl)amino-meth-yl]phenolate anion [N-Ag-N = 171.8 (1)°] and the terminal O atom of the other anion [Ag-O = 2.606 (3) Å]. A pair of 2-[(pyrimidin-2-yl)amino-meth-yl]phenolate anions link the two Ag(I) atoms to form the dinuclear compound. In the crystal, adjacent dinuclear mol-ecules are linked to the lattice water mol-ecules, generating an O-H⋯O- and N-H⋯O-connected three-dimensional network. In the crystal, the hy-droxy H atom is disordered over two positions in a 1:1 ratio; one half-occupancy H atom is connected to one hy-droxy group, whereas the other half-occupancy H atom is connected to another hy-droxy group.

  6. Preparation and optimization of pyrazolo[1,5-a]pyrimidines as new potent PDE4 inhibitors.

    Science.gov (United States)

    Le Roux, Jacques; Leriche, Caroline; Chamiot-Clerc, Philippe; Feutrill, John; Halley, Frank; Papin, David; Derimay, Nathalie; Mugler, Christelle; Grépin, Claudine; Schio, Laurent

    2016-01-15

    A new series of pyrazolo[1,5-a]pyrimidines exemplified by compound 1, has been identified with moderate activity (IC50=165nM), following GSK256066 rescaffolding. Compound 1 optimization at positions 2, 3, 6 and 7 gave compound 10 with high in vitro activity (IC50=0.7nM). Modeling studies based on the PDB structure 3GWT with compound 5 showed the expected overlay with the carboxamide, the aryl moiety and the sulfone. Cyclisation of the primary amide to the 5 position of the pyrazolo[1,5-a]pyrimidines scaffold afforded compounds 15 and 16 with 200-fold enhancement in activity and cellular potency. Copyright © 2015 Elsevier Ltd. All rights reserved.

  7. Probing mechanism of α-formylketene dithioacetal towards the facile formation of functionalized pyrimidines: A structural approach

    Science.gov (United States)

    Joy, Monu; Adeniyi, Adebayo A.; Mathews, Annie; Mathew, Bijo; Prasanth, S.; Soliman, Mohmoud E. S.; Malayan, Jalaja J.; Anabha, E. R.

    2017-01-01

    α-Formylketene dithioacetal is an active precursor for the synthesis of a variety of organic compounds including pyrimidines and its functionalized materials. The present study deals with the structural versatility of a solid representative compound from the family of α-formylketene dithioacetal to the formation of functionalized pyrimidines derivatives through experimental as well as theoretical methods. 2-(3,4-dimethoxybenzoyl)-3,3-bis(methylsulfanyl)prop-2-enal, the representative compound was synthesized with a reported protocol and characterized through spectral methods. The complete three dimensional solid state structural studies were carried out utilizing single crystal X-ray crystallographic technique along with theoretical methods like classical and accelerated molecular dynamics simulation. Various quantum chemical parameters were also discussed to reveals the complete molecular geometry and reactivity of designated compound.

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

    DEFF Research Database (Denmark)

    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 alter...

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

    Directory of Open Access Journals (Sweden)

    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.

  10. Structure-based discovery of novel 4,5,6-trisubstituted pyrimidines as potent covalent Bruton's tyrosine kinase inhibitors.

    Science.gov (United States)

    Zou, Yi; Xiao, Jianhu; Tu, Zhengchao; Zhang, Yingyi; Yao, Kun; Luo, Minghao; Ding, Ke; Zhang, Yihua; Lai, Yisheng

    2016-07-01

    A series of novel 4,5,6-trisubstituted pyrimidines were designed as potent covalent Bruton's tyrosine kinase (BTK) inhibitors based on the structure of ibrutinib by using a ring-opening strategy. Among these derivatives, compound I1 exhibited the most potent inhibitory activity with an IC50 value of 0.07μM. The preliminary structure-activity relationship was discussed and the primary amino group at the C-4 position of pyrimidine was crucial for maintaining BTK activity. Furthermore, molecular dynamics simulations and binding free energy calculations were performed for three inhibitor-BTK complexes to determine the probable binding model, which provided a comprehensive guide for further structural modification and optimization. Copyright © 2016 Elsevier Ltd. All rights reserved.

  11. Synthesis, Characterization and Biological Evaluation of Some Novel 2-Pyrazoline Analogues with Amino Pyrimidine Moiety as Potential Antimicrobial Agents

    Directory of Open Access Journals (Sweden)

    Y. A. Hatwar

    2016-05-01

    Full Text Available In pursuit to synthesize the molecules with enhanced biological activities, efforts have been made to accommodate 2-pyrazoline and amino pyrimidine moieties in a single molecular framework. In the present study some novel 2-pyrazoline analogues with amino pyrimidine moiety IV(a-k have been synthesized by refluxing N-substituted chalcone 2-pyrazoline (III with guanidinium carbonate. The chemical structures of the compounds were proved by elemental analysis, IR, 1H NMR, 13C NMR and mass spectrometric data. The synthesized compounds were screened for their anti-bacterial and anti-fungal activities against four bacterial and two fungal strains comparable to the reference standard ciprofloxacin and flucanozole respectively. Some of the compounds showed promising activity and proved that pyrazolines are found to be interesting lead molecules for further synthesis as antimicrobial agents.

  12. Decode the Sodium Label Lingo

    Science.gov (United States)

    ... For Preschooler For Gradeschooler For Teen Decode the Sodium Label Lingo Published January 24, 2013 Print Email Reading food labels can help you slash sodium. Here's how to decipher them. "Sodium free" or " ...

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

    Directory of Open Access Journals (Sweden)

    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.

  14. Facile Syntheses of New Pyrazolo[1,5-a] pyrimidines Derivatives via Reactions of Enaminones with Aminopyrazole

    Institute of Scientific and Technical Information of China (English)

    LI Ming; WANG Shu-wen; WEN Li-rong; KE Zi-qin

    2005-01-01

    Ethyl 7-aryl-2-benzylthiopyrazolo [ 1,5-a ] pyrimidine-3-carboxylates (3a-3f) were conveniently synthesized through the reactions of enaminones with 5-amino-3-benzylthio-4-ethoxycarbonyl-1H-pyrazole in good yields and high regioselectivity. The structures of the new compounds were fully characterized by spectroscopic measurments, elemental analysis and X-ray diffraction analysis. A plausible reaction mechanism for the formation of the title compounds was also presented.

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

    Institute of Scientific and Technical Information of China (English)

    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.

  16. Potentiometric investigation of acid-base equilibria of two newv pyrimidine derivatives in various methanol–water media

    Directory of Open Access Journals (Sweden)

    HASAN KILIÇ

    2006-01-01

    Full Text Available The acid-base properties of 1-amino-5-benzoyl-4-phenyl-1H-pyrimidine-2-one (L1 and 1-amino-5-benzoyl-4-phenyl-1H-pyrimidine-2-thione (L2 were investigated potentiometrically at an ionic strength of 0.10M(LiCl in 19.8, 33.6 and 55.9 % (v/v methanol–water mixtures at 25.0 ± 0.1 ºC. The apparent dissociation constants (psKa were calculated for the di-protonated form (L1H2+2 and L2H2+2 of pyrimidine bases, using a software package TITFIT, which were then extrapolated to pure water to derive the dissociation constants in aqueous solution (pKa. The aqueous pKa constants were found to be: L1, pKa1 = 3.76 and pKa2 = 6.95; L2, pKa1 = 3.57 and pKa1 = 6.90. At pH 2.00, the dominant species in solution were the protonated form of the amino group substituted at the 1-position, while at a pH around 5.00, they were the protonated form of the pyrimidine ring nitrogen at the 3-position. An effect of intramolecular hydrogen bonding on the psKa values was observed with L1 but not L2. The effects ofmolecular structure and solvent medium on the psKa values are also discussed.

  17. Novel N-(pyrimidin-4-ylthiazol-2-amine derivatives as dual-action hypoglycemic agents that activate GK and PPARγ

    Directory of Open Access Journals (Sweden)

    Hui-peng Song

    2011-10-01

    Full Text Available A series of novel N-(pyrimidin-4-ylthiazol-2-amine derivatives have been synthesized and evaluated as glucokinase (GK activators. Ethyl 2-(6-(4-(2-hydroxyethylpiperazin-1-yl-2-methylpyrimidin-4-yl-aminothiazole-5-carboxylate was found to be a potent dual-acting hypoglycemic agent activating both GK and PPARγ. When given orally to normal mice, the compound demonstrated significant efficacy in decreasing the glucose level after oral glucose loading.

  18. Labelling GM-free Products

    DEFF Research Database (Denmark)

    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...

  19. Food Labels Tell the Story!

    Science.gov (United States)

    ... 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 ...

  20. Modeling the effects of labeling

    DEFF Research Database (Denmark)

    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...

  1. Scaffolding Visitors' Learning through Labels

    Science.gov (United States)

    Wang, Joyce; Yoon, Susan

    2013-01-01

    In museum literature, labels have been found to increase visitor learning and contribute to greater cognitive gains. In this study, we seek to understand how various labels support the visitors' learning experience, and specifically in regards to conceptual and cognitive learning. We investigated the increasing use of three types of labels (visual…

  2. A facile environment-friendly one-pot two-step regioselective synthetic strategy for 3,7-diarylpyrazolo[1,5-a]pyrimidines related to zaleplon and 3,6-diarylpyrazolo[1,5-a]pyrimidine-7-amines assisted by KHSO[Formula: see text] in aqueous media.

    Science.gov (United States)

    Devi, Asem Satyapati; Kaping, Shunan; Vishwakarma, Jai Narain

    2015-11-01

    3-Aminopyrazoles required for the synthesis of pyrazolo[1,5-a]pyrimidines were obtained by the reaction of enaminonitriles with hydrazine hydrate. The resulting aminopyrazoles are reacted with formylated acetophenones under reflux at [Formula: see text] assisted by KHSO[Formula: see text] in aqueous media to form regioselectively 3,7-diarylpyrazolo[1,5-a]pyrimidines and 3,6-diarylpyrazolo[1,5-a]pyrimidine-7-amines. X-ray crystallography of selected compounds 5b and 7i further confirmed the regioselective formation of these products.

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

    Science.gov (United States)

    Kelemen, Linda E.; Terry, Kathryn L.; Goodman, Marc T.; Webb, Penelope M.; Bandera, Elisa V.; McGuire, Valerie; Rossing, Mary Anne; Wang, Qinggang; Dicks, Ed; Tyrer, Jonathan P.; Song, Honglin; Kupryjanczyk, Jolanta; Dansonka-Mieszkowska, Agnieszka; Plisiecka-Halasa, Joanna; Timorek, Agnieszka; Menon, Usha; Gentry-Maharaj, Aleksandra; Gayther, Simon A.; Ramus, Susan J.; Narod, Steven A.; Risch, Harvey A.; McLaughlin, John R.; Siddiqui, Nadeem; Glasspool, Rosalind; Paul, James; Carty, Karen; Gronwald, Jacek; Lubiński, Jan; Jakubowska, Anna; Cybulski, Cezary; Kiemeney, Lambertus A.; Massuger, Leon F. A. G.; van Altena, Anne M.; Aben, Katja K. H.; Olson, Sara H.; Orlow, Irene; Cramer, Daniel W.; Levine, Douglas A.; Bisogna, Maria; Giles, Graham G.; Southey, Melissa C.; Bruinsma, Fiona; Kjær, Susanne Krüger; Høgdall, Estrid; Jensen, Allan; Høgdall, Claus K.; Lundvall, Lene; Engelholm, Svend-Aage; Heitz, Florian; du Bois, Andreas; Harter, Philipp; Schwaab, Ira; Butzow, Ralf; Nevanlinna, Heli; Pelttari, Liisa M.; Leminen, Arto; Thompson, Pamela J.; Lurie, Galina; Wilkens, Lynne R.; Lambrechts, Diether; Van Nieuwenhuysen, Els; Lambrechts, Sandrina; Vergote, Ignace; Beesley, Jonathan; Fasching, Peter A.; Beckmann, Matthias W.; Hein, Alexander; Ekici, Arif B.; Doherty, Jennifer A.; Wu, Anna H.; Pearce, Celeste L.; Pike, Malcolm C.; Stram, Daniel; Chang-Claude, Jenny; Rudolph, Anja; Dörk, Thilo; Dürst, Matthias; Hillemanns, Peter; Runnebaum, Ingo B.; Bogdanova, Natalia; Antonenkova, Natalia; Odunsi, Kunle; Edwards, Robert P.; Kelley, Joseph L.; Modugno, Francesmary; Ness, Roberta B.; Karlan, Beth Y.; Walsh, Christine; Lester, Jenny; Orsulic, Sandra; Fridley, Brooke L.; Vierkant, Robert A.; Cunningham, Julie M.; Wu, Xifeng; Lu, Karen; Liang, Dong; Hildebrandt, Michelle A.T.; Weber, Rachel Palmieri; Iversen, Edwin S.; Tworoger, Shelley S.; Poole, Elizabeth M.; Salvesen, Helga B.; Krakstad, Camilla; Bjorge, Line; Tangen, Ingvild L.; Pejovic, Tanja; Bean, Yukie; Kellar, Melissa; Wentzensen, Nicolas; Brinton, Louise A.; Lissowska, Jolanta; Garcia-Closas, Montserrat; Campbell, Ian G.; Eccles, Diana; Whittemore, Alice S.; Sieh, Weiva; Rothstein, Joseph H.; Anton-Culver, Hoda; Ziogas, Argyrios; Phelan, Catherine M.; Moysich, Kirsten B.; Goode, Ellen L.; Schildkraut, Joellen M.; Berchuck, Andrew; Pharoah, Paul D.P.; Sellers, Thomas A.; Brooks-Wilson, Angela; Cook, Linda S.; Le, Nhu D.

    2014-01-01

    Scope We re-evaluated previously reported associations between variants in pathways of one-carbon (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 ratios (OR) for 446 genetic variants were estimated among 13,410 OC cases and 22,635 controls and among 2,281 cases and 3,444 controls with folate information. Following multiple testing correction, the most significant main effect associations were for DPYD variants rs11587873 (OR=0.92, P=6x10−5) and rs828054 (OR=1.06, P=1x10−4). Thirteen variants in the pyrimidine metabolism genes, DPYD, DPYS, PPAT and TYMS, also interacted significantly with folate in a multi-variant analysis (corrected P=9.9x10−6) but collectively explained only 0.2% of OC risk. Although no other associations were significant after multiple testing correction, variants in SHMT1 in one-carbon transfer, previously reported with OC, suggested lower risk at higher folate (Pinteraction=0.03-0.006). Conclusions Variation in pyrimidine metabolism genes, particularly DPYD, which was previously reported to be associated with OC, may influence risk; however, stratification by folate intake is unlikely to modify disease risk appreciably in these women. SHMT1 SNP-byfolate interactions are plausible but require further validation. Polymorphisms in selected genes in purine metabolism were not associated with OC. PMID:25066213

  4. [Distribution of pyrimidine blocks in the DNA of Brevibacterium linens, Arthrobacter globiformis, Nocardia corallina and Nocardia rubra].

    Science.gov (United States)

    Eroshina, N V; Golovlev, E L; Geĭdarov, T G; Bur'ianov, Ia I

    1975-01-01

    The nucleotide composition and the frequency of pyrimidine blocks were studied in DNA of the following bacteria: Brevibacterium linens (Weignamm, 1910) Breed, 1953; Arthrobacter globiformis (Conn, 1928) Conn et Dimmick, 1947; Nocardia corallina (Bergey et al., 1923) Waksman et Henrici, 1948; Nocardia rubra (Krassilnikov, 1949) Waksman et Henrici, 1948. These organisms are classed by some microbiologists as mycobacteria (the Mycobacteriaceae family) while other authors regard them as representatives of three families belonging to two orders. About 60 percent of all pyrimidines in DNA of these bacteria are found in the sequences pur-pyr-pur and pur-pyr-pyr-pur, the number of dipyrimidines being higher than the amount of monopyrimidine nucleotides. The content of dipyrimidine nucleotides in DNA of Nocardia corallina and Nocardia rubra is higher (16.8 mole %) than the content of dipyrimidine blocks in DNA of Brevibacterium linens and Arthrobacter globiformis, in which the quantity of dipyrimidines is almost the same (13.9 and 14.4 mole %). A new characteristic, the selected mean value, is suggested to evaluate differences in the distribution of pyrimidines in DNA.

  5. Pyrimidine dimer formation and germination of UV-irradiated spores of Dictyostelium discoideum NC-4 and. gamma. s-13

    Energy Technology Data Exchange (ETDEWEB)

    Nozu, K.; Ohnishi, T.; Okaichi, K. (Nara Medical Univ., Kashihara (Japan))

    1982-04-01

    Survival, UV-photoproducts and germination of UV-irradiated spores of Dictyostelium discoideum were studied on two strains, NC-4 and ..gamma..s-13. The spores of NC-4 are about 35 times more resistant to UV than ..gamma..s-13 spores at 10% survival. Pyrimidine dimers were formed in UV-irradiated spores in both strains. No photoproducts other than pyrimidine dimers were detected. The formation of pyrimidine dimers in spores was about 2% in both strains at 800 J/m/sup 2/. In the germination of spores, the conversion of spores into swollen spores was not affected by UV in both strains, but the emergence of amoebae from the swollen spores was suppressed, which was more distinctive in ..gamma..s-13 spores than in NC-4 spores. The emerged amoebae from the UV-irradiated NC-4 spores were viable, while those from the ..gamma..s-13 spores were inviable even when they succeeded in emergence.

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

    Directory of Open Access Journals (Sweden)

    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.

  7. Radiosynthesis and Preclinical Evaluation of [(18)F]F-DPA, A Novel Pyrazolo[1,5a]pyrimidine Acetamide TSPO Radioligand, in Healthy Sprague Dawley Rats.

    Science.gov (United States)

    Keller, Thomas; Krzyczmonik, Anna; Forsback, Sarita; Picón, Francisco R López; Kirjavainen, Anna K; Takkinen, Jatta; Rajander, Johan; Cacheux, Fanny; Damont, Annelaure; Dollé, Frédéric; Rinne, Juha O; Haaparanta-Solin, Merja; Solin, Olof

    2017-01-12

    Many neurological conditions result in the overexpression of the translocator protein 18 kDa (TSPO), today recognized as a biomarker for microglial activation and neuroinflammation imaging. The pyrazolo[1,5-a]pyrimidine acetamides are a particularly attractive class of TSPO-specific ligands, prompting the development of several positron emission tomography (PET) radiotracers. This includes F-DPA, a recently reported fluorinated ligand (K i = 1.7 nM), wherein the fluorine atom is directly linked to the phenyl moiety without the presence of an alkyl or alkoxy spacer chain. Reported here is the preparation of [(18)F]F-DPA using [(18)F]Selectfluor bis(triflate) and the preliminary evaluation of [(18)F]F-DPA in healthy rats. Its metabolic profile and biodistribution in rats are compared with that of [(18)F]DPA-714, a closely related structure. [(18)F]F-DPA was synthesized by electrophilic fluorination using [(18)F]Selectfluor bis(triflate), [(18)F]DPA-714 was synthesized by conventional nucleophilic fluorination. The biodistribution of both radiotracers was compared in Sprague Dawley rats. Radiometabolites of both radiotracers in plasma and brain homogenates were analyzed by radioTLC. The radiochemical yield of [(18)F]F-DPA was 15 ± 3 % and the specific activity was 7.8 ± 0.4 GBq/μmol. The radiochemical purity exceeded 99 %. The in vivo time activity curves of [(18)F]F-DPA demonstrate rapid entry into the brain and a concentration equilibrium at 20-30 min after injection. The metabolic profiles at 90 min after radiotracer injection in the plasma show that unchanged [(18)F]F-DPA and [(18)F]DPA-714 account for 28.3 ± 6.4 and 11.1 ± 2.6 % of the remaining radioactivity, respectively. In the brain, unchanged [(18)F]F-DPA accounts for 93.5 ± 2.8 % of the radioactivity; whereas for [(18)F]DPA-714, this value is 53.6 ± 1.6 %. [(18)F]Selectfluor bis(triflate) was successfully used to label F-DPA with fluorine-18. The labeling

  8. Measurement of oxidative damage at pyrimidine bases in gamma-irradiated DNA.

    Science.gov (United States)

    Douki, T; Delatour, T; Paganon, F; Cadet, J

    1996-01-01

    Oxidized nucleobases represent one of the main classes of damage induced in DNA by ionizing radiation. Emphasis was placed in this work on the measurement of four oxidized pyrimidine bases, including 5-(hydroxymethyl)uracil (5-HMUra), 5-formyluracil (5-ForUra), 5-hydroxycytosine (5-OHCyt), and 5-hydroxyuracil (5-OHUra), in isolated DNA upon exposure to gamma radiation in aerated aqueous solution. For this purpose, both high performance liquid chromatography associated with electrochemical detection (HPLC-EC) and gas chromatography coupled to mass spectrometry (GC-MS) were used. Conditions of hydrolysis of the N-glycosidic bond were carefully checked in order to achieve a quantitative release of the lesions. We showed that 60% formic acid treatment leads to the decomposition of the four lesions studied. On the other hand, hydrolysis based on the use of either 88% formic acid or 70% hydrogen fluoride in pyridine (HF/Pyr) allowed the quantitative release of the modified bases, with the exception of 5-HMUra when the latter reagent was utilized. A dose course study of the radiation-induced formation of 5-HMUra and 5-ForUra in DNA by using the GC-MS assay showed that the latter lesion was produced in a 2.1-fold higher yield than the former one. HF/Pyr and 88% formic acid hydrolysis provided similar results for 5-ForUra, indicating the reliability of both techniques for the measurement of this lesion. For 5-OHUra and 5-OHCyt, the level of modification determined by GC-MS analysis was higher after 88% formic acid treatment than upon HF/Pyr hydrolysis. When DNA was enzymatically digested and analyzed by HPLC-EC for 5-OHdCyd and 5-OHdUrd, the results were very close to those obtained by GC-MS following HF/Pyr treatment. It was concluded that additional amounts of both 5-OHUra and 5-OHCyt are produced during the 88% formic acid treatment from radiation-induced 5,6-saturated pyrimidine precursors. It is likely that cytosine and uracil diols are involved in this reaction. The

  9. Efficacy of a pyrimidine derivative to control spot disease on Solanum melongena caused by Alternaria alternata

    Directory of Open Access Journals (Sweden)

    Nemat M. Hassan

    2013-07-01

    Full Text Available The pyrimidine derivative (4,6-dimethyl-N-phenyldiethyl pyrimidine, DPDP was tested as a foliar spray fungicide at 50 mg l−1 for protection of eggplant (Solanum melongena from spot disease caused by Alternaria alternata. Varied concentrations of DPDP (10–50 mg l−1 differentially inhibited mycelial growth, conidial count and conidial germination of A. alternata growth in vitro; the magnitude of inhibition increased with increasing concentration. In vivo, an experiment was conducted in pots using a complete block randomized design and repeated twice with three replications and four treatments (control, A. alternata alone, DPDP alone and combination of DPDP and A. alternata for 5 weeks (1 plant in pot × 3 pots per set (3 replications per treatment × 4 sets (4 treatments × 5 weeks × 2 experimental repetitions = 120 pots. In this experiment, 10-day-old eggplant seedlings were transplanted in pots and then inoculated with A. alternata, DPDP or their combination 1 week later. Leaves of the A. alternata-infected eggplant suffered from chlorosis, necrosis and brown spots during the subsequent 5 weeks. Disease intensity was obvious in infected leaves but withdrawn by DPDP. There were relationships between incidence and severity, greater in plant leaves infected A. alternata alone and diminished with the presence of DPDP. Moreover, the infection resulted in reductions in growth, decreases in contents of anthocyanins, chlorophylls, carotenoids and thiols as well as inhibitions in activities of superoxide dismutase (SOD, glutathione peroxidase (GPX and glutathione-S-transferase (GST. Nonetheless, the application of DPDP at 50 mg led to a recovery of the infected eggplant; the infection-induced deleterious effects were mostly reversed by DPDP. However, treatment with DPDP alone seemed with no significant impacts. Due to its safe use to host and the inhibition for the pathogen, DPDP could be suggested as an efficient fungicide for

  10. Map labeling and its generalizations

    Energy Technology Data Exchange (ETDEWEB)

    Doddi, S. [New Mexico Univ., Albuquerque, NM (United States). Dept. of Computer Science]|[Los Alamos National Lab., NM (United States); Marathe, M.V. [Los Alamos National Lab., NM (United States); Mirzaian, A. [York Univ., Toronto, ON (Canada). Dept. of Computer Science; Moret, B.M.E. [New Mexico Univ., Albuquerque, NM (United States). Dept. of Computer Science; Zhu, B. [City Univ. of Hong Kong (Hong Kong). Dept. of Computer Science]|[Los Alamos National Lab., NM (United States)

    1997-01-01

    Map labeling is of fundamental importance in cartography and geographical information systems and is one of the areas targeted for research by the ACM Computational Geometry Impact Task Force. Previous work on map labeling has focused on the problem of placing maximal uniform, axis-aligned, disjoint rectangles on the plane so that each point feature to be labeled lies at the corner of one rectangle. Here, we consider a number of variants of the map labeling problem. We obtain three general types of results. First, we devise constant-factor polynomial-time-approximation algorithms for labeling point features by rectangular labels, where the feature may lie anywhere on the boundary of its label region and where labeling rectangles may be placed in any orientation. These results generalize to the case of elliptical labels. Secondly, we consider the problem of labeling a map consisting of disjoint rectilinear fine segments. We obtain constant-factor polynomial-time approximation algorithms for the general problem and an optimal algorithm for the special case where all segments are horizontal. Finally, we formulate a bicriteria version of the map-labeling problem and provide bicriteria polynomial- time approximation schemes for a number of such problems.

  11. Linerless label device and method

    KAUST Repository

    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.

  12. 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

    Energy Technology Data Exchange (ETDEWEB)

    Dayie, T. Kwaku, E-mail: dayie@umd.edu; Thakur, Chandar S. [University of Maryland, Department of Chemistry and Biochemistry, Center for Biomolecular Structure and Organization (United States)

    2010-05-15

    Escherichia coli (E. coli) is a versatile organism for making nucleotides labeled with stable isotopes ({sup 13}C, {sup 15}N, and/or {sup 2}H) 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-{sup 13}C-glycerol and {sup 15}N-ammonium sulfate in Studier minimal medium enables labeling at sites useful for NMR spectroscopy. However, {sup 13}C-sodium formate combined with {sup 13}C-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 {sup 1}J{sub C5C6} 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 {sup 13}C-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 {sup 15}N-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.

  13. Pyrimidines and the X-ray response of Tribolium confusum Duval.

    Science.gov (United States)

    Hogan, G R

    1968-11-01

    Radiosensitizing effects of incorporation into DNA of the halogenated pyrimidines 5-bromouracil or 5-iodouracil, or their nucleosides (BUdR and IUdR), have been demonstrated in a variety of cell types. The results indicate that these antimetabolites influence lethality in x-irradiated adult Tribolium. At relatively low concentrations in the medium, BUdR and IUdR exhibit toxicity 3 to 5 weeks after transfer of beetles to analog-containing medium. Toxicity of IUdR on nonirradiated adults is less pronounced than that of BUdR and is slower to develop. Analog-treated Tribolium exposed to 7 kR, which is sublethal for adults in normal medium, die much earlier than those treated with analog alone or with lethal doses of x-rays alone. Transfer of beetles to normal medium after 3 weeks or less in the presence of analog virtually eliminates lethality attributable to the analog. X-irradiation at the time of transfer, however, leads to high mortality, and the amount of mortality appears to be a function of the duration of analog treatment. Insects grown in medium containing uracil or thymine exhibit the same survival as those reared in unsupplemented medium. Two weeks after 7 kR of irradiation a sharp decline in survival is seen in both uracil- and thymine-treated groups.

  14. Wavelength-dependent ultraviolet induction of cyclobutane pyrimidine dimers in the human cornea.

    Science.gov (United States)

    Mallet, Justin D; Rochette, Patrick J

    2013-08-01

    Exposition to ultraviolet (UV) light is involved in the initiation and the progression of skin cancer. The genotoxicity of UV light is mainly attributed to the induction of cyclobutane pyrimidine dimers (CPDs), the most abundant DNA damage generated by all UV types (UVA, B and C). The human cornea is also exposed to the harmful UV radiations, but no UV-related neoplasm has been reported in this ocular structure. The probability that a specific DNA damage leads to a mutation and eventually to cellular transformation is influenced by its formation frequency. To shed light on the genotoxic effect of sunlight in the human eye, we have analyzed CPD induction in the cornea and the iris following irradiation of ex vivo human eyes with UVA, B or C. The extent of CPD induction was used to establish the penetrance of the different UV types in the human cornea. We show that UVB- and UVC-induced CPDs are concentrated in the corneal epithelium and do not penetrate deeply beyond this corneal layer. On the other hand, UVA wavelengths penetrate deeper and induce CPDs in the entire cornea and in the first layers of the iris. Taken together, our results are undoubtedly an important step towards better understanding the consequences of UV exposure to the human eye.

  15. Purine and pyrimidine composition in 5S rRNA and its mutational significance

    Directory of Open Access Journals (Sweden)

    Subacius Sandra Maria Rodrigues

    1998-01-01

    Full Text Available Variations observed in 5S rRNA base compositions are almost entirely due to fixation of point mutations. As a consequence, 5S rRNA size has remained relatively constant during evolution and, therefore, dependencies among the four bases can be predicted. In order to characterize the nature and to determine the degree of such dependencies, correlation analysis followed by principal component factorial analysis was conducted on a large sample of 5S rRNA sequences. The results show that the purine and pyrimidine contents tend to remain constant, so that A + G = Kpur and C + U = Kpyr. The composition of the four bases expressed now by Kpur/Kpyr relationships is also constant (Ks. These relationships imply that the behavior of the mutations in the variable sites of the molecule follows rules imposed by the chemical nature of the bases involved. Consequently, transition mutations would be more favored than substitutions in transversion sites and also than insertion-deletion (rare in 5S rRNAs, since transitions would not significantly alter the values of the Ks-index.

  16. Apigenin prevents ultraviolet-B radiation induced cyclobutane pyrimidine dimers formation in human dermal fibroblasts.

    Science.gov (United States)

    Britto, S Mary; Shanthakumari, D; Agilan, B; Radhiga, T; Kanimozhi, G; Prasad, N Rajendra

    2017-09-01

    Exposure to solar ultraviolet-B (UVB) radiation leads to the formation of cyclobutane pyrimidine dimers (CPDs). We investigated the protective effect of apigenin against UVB-induced CPDs formation in human dermal fibroblasts cells (HDFa). For this purpose, HDFa cells were treated with apigenin (15μM) prior to UVB irradiation (20mJ/cm(2)); DNA damage and subsequent molecular end points were observed. Exposure to UVB radiation increased significant CPDs formation in HDFa cells and the frequencies of CPDs were reduced by treatment with apigenin (15μM). UVB-induced CPDs downregulates the expression of nucleotide excision repair (NER) genes such as xeroderma pigmentosum complementation group C, B, G and F (XPC, XPB, XPG and XPF), transcription factor II human (TFIIH) and excision repair cross-complementation group 1 (ERCC1) in HDFa cells. Conversely, apigenin treatment restored UVB-induced loss of NER proteins in HDFa cells, which indicates its preventive effect against CPDs formation. Besides, single low dose UVB-exposure induced nuclear fragmentation, apoptotic frequency and apoptotic proteins expression (Bax and Caspase-3) have been prevented by the apigenin pretreatment. Furthermore, apigenin exhibits strong UV absorbance property and showed 10.08 SPF value. Thus, apigenin can protect skin cells against UVB-induced CPDs formation probably through its sunscreen effect. Hence, apigenin can be considered as an effective protective agent against UV induced skin damages. Copyright © 2017 Elsevier B.V. All rights reserved.

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

    Science.gov (United States)

    Fulfer, K D; Hardy, D; Aguilar, A A; Poliakoff, E D

    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.

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

  19. Synthesis and biological evaluation of oxindole linked indolyl-pyrimidine derivatives as potential cytotoxic agents.

    Science.gov (United States)

    Prajapti, Santosh Kumar; Nagarsenkar, Atulya; Guggilapu, Sravanthi Devi; Gupta, Keshav Kumar; Allakonda, Lingesh; Jeengar, Manish Kumar; Naidu, V G M; Babu, Bathini Nagendra

    2016-07-01

    In our endeavor towards the development of effective cytotoxic agents, a series of oxindole linked indolyl-pyrimidine derivatives were synthesized and characterized by IR, (1)H NMR, (13)C NMR and Mass spectral analysis. All the newly synthesized target compounds were assessed against PA-1 (ovarian), U-87MG (glioblastoma), LnCaP (prostate), and MCF-7 (Breast) cancer cell lines for their cytotoxic potential, with majority of them showing inhibitory activity at low micro-molar concentrations. Significantly, compound 8e was found to be most potent amongst all the tested compounds with an IC50 value of (2.43±0.29μM) on PA-1 cells. The influence of the most active cytotoxic compound 8e on the cell cycle distribution was assessed on the PA-1 cell line, exhibiting a cell cycle arrest at the G2/M phase. Moreover, acridine orange/ethidium bromide staining and annexin V binding assay confirmed that compound 8e can induce cell apoptosis in PA-1 cells. These preliminary results persuade further investigation on the synthesized compounds aiming to the development of potential cytotoxic agents.

  20. Investigating the role of vibrational excitation in simulating charged-particle tracks in liquid pyrimidine

    Science.gov (United States)

    Brunger, Michael J.; Ratnavelu, Kuru; Buckman, Stephen J.; Jones, Darryl B.; Muñoz, Antonio; Blanco, Francisco; García, Gustavo

    2016-03-01

    We report on our results of a study into the sensitivity of charged-particle (electron) track simulations in liquid pyrimidine, to the vibrational cross sections and vibrational energy loss distribution function employed in those simulations. We achieve this by repeating the earlier investigation of Fuss et al. [J. Appl. Phys. 117, 214701 (2015)], but now incorporating more accurate data for the vibrational integral cross sections and the energy loss distribution function that have recently become available. We find that while changes in absorbed dose or particle range are quite minor, due to the energy transferred via vibrational excitations being low in comparison to that for other processes such as ionisation, at the very end of the tracks, where non-ionizing interactions dominate, the significantly large numbers of vibrational excitation processes increases the electrons' ability to induce other effects (e.g. sample heating, bond breaking and radical formation) that might cause damage. 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.

  1. Structural Insight into the Core of CAD, the Multifunctional Protein Leading De Novo Pyrimidine Biosynthesis.

    Science.gov (United States)

    Moreno-Morcillo, María; Grande-García, Araceli; Ruiz-Ramos, Alba; Del Caño-Ochoa, Francisco; Boskovic, Jasminka; Ramón-Maiques, Santiago

    2017-06-06

    CAD, the multifunctional protein initiating and controlling de novo biosynthesis of pyrimidines in animals, self-assembles into ∼1.5 MDa hexamers. The structures of the dihydroorotase (DHO) and aspartate transcarbamoylase (ATC) domains of human CAD have been previously determined, but we lack information on how these domains associate and interact with the rest of CAD forming a multienzymatic unit. Here, we prove that a construct covering human DHO and ATC oligomerizes as a dimer of trimers and that this arrangement is conserved in CAD-like from fungi, which holds an inactive DHO-like domain. The crystal structures of the ATC trimer and DHO-like dimer from the fungus Chaetomium thermophilum confirm the similarity with the human CAD homologs. These results demonstrate that, despite being inactive, the fungal DHO-like domain has a conserved structural function. We propose a model that sets the DHO and ATC complex as the central element in the architecture of CAD. Copyright © 2017 Elsevier Ltd. All rights reserved.

  2. Divergent Functions Through Alternative Splicing: The Drosophila CRMP Gene in Pyrimidine Metabolism, Brain, and Behavior

    Science.gov (United States)

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

    2012-01-01

    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

  3. CONSTRUCTION OF 3D MODEL FOR CYCLOBUTANE PYRIMIDINE (CPD PHOTOLYASE FROM CHLORELLA PYRENOIDOSA

    Directory of Open Access Journals (Sweden)

    Vinod Rishi

    2010-08-01

    Full Text Available Chlorella pyrenoidosa is a freshwater green alga and belongs to class Chlorophyceae, order Chlorellales and family Chlorellaceae. CPD photolyase is an enzyme found in Chlrella pyrnoidosa and responsible for repairing of DNA damages caused by UV radiations. The cyclobutane pyrimidine dimmer (CPDs and 6-4 pyrimidone photoproducts (6-4 PPs are major form of DNA damages and these damages are caused by various physical and chemical agents occurs in the environment such as UV and ionizing radiations, chemical mutagens fungal and bacterial toxins, and free radicals or alkalizing agents produced by metabolism. Mostly DNA damages induced by UV radiations, about 75% cyclobutane pyrimidinedimers (CPDs and rest 6-4 photoproducts (6-4PPs.If these are not repaired then both dimmers may be block transcription and DNA replication. CPD photolyase binds to the DNA and prevent the production of CPDs and 6-4 PPs. The three dimensional structure of CPD photolyase of Chlorella pyrenoidosa is not available for the further investigation , so it is required to generate a computational model by using Modeler 9v3 program. The quality of modeled structure is verified through various online (ProSA as well as offline (Procheck, Swiss PDB viewer tools. This protein may be useful in prevention of skin cancer.

  4. Photochemical Hydrogen Abstraction and Electron Transfer Reactions of Tetrachlorobenzoquinone with Pyrimidine Nucleobases

    Institute of Scientific and Technical Information of China (English)

    Kun-hui Liu; Li-dan Wu; Xiao-ran Zou; Wen Yang; Qian Du; Hong-mei Su

    2011-01-01

    Pentachlorophenol,a widespread environmental pollutant that is possibly carcinogenic to humans,is metabolically oxidized to tetrachloroquinone (TCBQ) which can result in DNA damage.We have investigated the photochemical reaction dynamics of TCBQ with two pyrimidine type nucleobases (thymine and uracil) upon UVA (355 nm) excitation using the technique of nanosecond time-resolved laser flash photolysis.It has been found that 355 nm excitation populates TCBQ molecules to their triplet state 3TCBQ*,which are highly reactive towards thymine or uracil and undergo two parallel reactions,the hydrogen abstraction and electron transfer,leading to the observed photoproducts of TCBQH.and TCBQ.- in transient absorption spectra.The concomitantly produced nucleobase radicals and radical cations are expected to induce a series of oxidative or strand cleavage damage to DNA afterwards.By characterizing the photochemical hydrogen abstraction and electron transfer reactions,our results provide potentially important molecular reaction mechanisms for understanding the carcinogenic effects of pentachlorophenol and its metabolites TCBQ.

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

  6. Double Variational Binding—(SMILES Conformational Analysis by Docking Mechanisms for Anti-HIV Pyrimidine Ligands

    Directory of Open Access Journals (Sweden)

    Mihai V. Putz

    2015-08-01

    Full Text Available Variational quantitative binding–conformational analysis for a series of anti-HIV pyrimidine-based ligands is advanced at the individual molecular level. This was achieved by employing ligand-receptor docking algorithms for each molecule in the 1,3-disubstituted uracil derivative series that was studied. Such computational algorithms were employed for analyzing both genuine molecular cases and their simplified molecular input line entry system (SMILES transformations, which were created via the controlled breaking of chemical bonds, so as to generate the longest SMILES molecular chain (LoSMoC and Branching SMILES (BraS conformations. The study identified the most active anti-HIV molecules, and analyzed their special and relevant bonding fragments (chemical alerts, and the recorded energetic and geometric docking results (i.e., binding and affinity energies, and the surface area and volume of bonding, respectively. Clear computational evidence was also produced concerning the ligand-receptor pocket binding efficacies of the LoSMoc and BraS conformation types, thus confirming their earlier presence (as suggested by variational quantitative structure-activity relationship, variational-QSAR as active intermediates for the molecule-to-cell transduction process.

  7. Double Variational Binding—(SMILES) Conformational Analysis by Docking Mechanisms for Anti-HIV Pyrimidine Ligands

    Science.gov (United States)

    Putz, Mihai V.; Dudaș, Nicoleta A.; Isvoran, Adriana

    2015-01-01

    Variational quantitative binding–conformational analysis for a series of anti-HIV pyrimidine-based ligands is advanced at the individual molecular level. This was achieved by employing ligand-receptor docking algorithms for each molecule in the 1,3-disubstituted uracil derivative series that was studied. Such computational algorithms were employed for analyzing both genuine molecular cases and their simplified molecular input line entry system (SMILES) transformations, which were created via the controlled breaking of chemical bonds, so as to generate the longest SMILES molecular chain (LoSMoC) and Branching SMILES (BraS) conformations. The study identified the most active anti-HIV molecules, and analyzed their special and relevant bonding fragments (chemical alerts), and the recorded energetic and geometric docking results (i.e., binding and affinity energies, and the surface area and volume of bonding, respectively). Clear computational evidence was also produced concerning the ligand-receptor pocket binding efficacies of the LoSMoc and BraS conformation types, thus confirming their earlier presence (as suggested by variational quantitative structure-activity relationship, variational-QSAR) as active intermediates for the molecule-to-cell transduction process. PMID:26295229

  8. Detection of UV-induced cyclobutane pyrimidine dimers by near-infrared spectroscopy and aquaphotomics.

    Science.gov (United States)

    Goto, Noriko; Bazar, Gyorgy; Kovacs, Zoltan; Kunisada, Makoto; Morita, Hiroyuki; Kizaki, Seiichiro; Sugiyama, Hiroshi; Tsenkova, Roumiana; Nishigori, Chikako

    2015-07-02

    Ultraviolet (UV) radiation causes cellular DNA damage, among which cyclobutane pyrimidine dimers (CPDs) are responsible for a variety of genetic mutations. Although several approaches have been developed for detection of CPDs, conventional methods require time-consuming steps. Aquaphotomics, a new approach based on near-infrared spectroscopy (NIRS) and multivariate analysis that determines interactions between water and other components of the solution, has become an effective method for qualitative and quantitative parameters measurement in the solutions. NIR spectral patterns of UVC-irradiated and nonirradiated DNA solutions were evaluated using aquaphotomics for detection of UV-induced CPDs. Groups of UV-irradiated and nonirradiated DNA samples were classified (87.5% accuracy) by soft independent modeling of class analogy (SIMCA). A precise regression model calculated from NIR water spectral patterns based on UVC doses (r Val = 0.9457) and the concentration of cis-syn cyclobutane thymine dimers (cis-syn TTs; r Val = 0.9993) was developed using partial least squares regression (PLSR), while taking advantage of water spectral patterns, particularly around 1400-1500 nm. Our results suggested that, in contrast to DNA, the formation of cis-syn TTs increased the strongly hydrogen bonded water. Additionally, NIRS could qualitatively and quantitatively detect cis-syn TTs in isolated DNA aqueous solutions upon UVC exposure.

  9. Pyrimidine-based compounds modulate CXCR2-mediated signaling and receptor turnover.

    Science.gov (United States)

    Ha, Helen; Neamati, Nouri

    2014-07-07

    Chemokine receptor CXCR2 is expressed on various immune cells and is essential for neutrophil recruitment and angiogenesis at sites of acute and chronic inflammation caused by tissue injury or infection. Because of its role in inflammation, it has been implicated in a number of immune-mediated inflammatory diseases such as psoriasis, arthritis, COPD, cystic fibrosis, asthma, and various types of cancer. CXCR2 and its ligands are up-regulated in cancer cells as well as the tumor microenvironment, promoting tumor growth, angiogenesis, and invasiveness. Although pharmaceutical companies have pursued the development of CXCR2-specific small-molecule inhibitors as anti-inflammatory agents within the last decades, there are currently no clinically approved CXCR2 inhibitors. Using a high-throughput, cell-based assay specific for CXCR2, we screened an in-house library of structurally diverse compounds and identified a class of pyrimidine-based compounds that alter CXCR2-mediated second messenger signaling. Our lead compound, CX797, inhibited IL8-mediated cAMP signaling and receptor degradation while specifically up-regulating IL8-mediated β-arrestin-2 recruitment. CX797 also inhibited IL8-mediated cell migration. Mechanistic comparison of CX797 and a previously reported CXCR2 inhibitor, SB265610, show these two classes of compounds have a distinct mechanism of action on CXCR2.

  10. From Label to Practice

    DEFF Research Database (Denmark)

    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...

  11. 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}

    Directory of Open Access Journals (Sweden)

    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.

  12. Synthesis of New Pyrazolo[1,5-a]pyrimidine, Triazolo[4,3-a]pyrimidine Derivatives, and Thieno[2,3-b]pyridine Derivatives from Sodium 3-(5-Methyl-1-phenyl-1H-pyrazol-4-yl-3-oxoprop-1-en-1-olate

    Directory of Open Access Journals (Sweden)

    Abdou O. Abdelhamid

    2013-01-01

    Full Text Available Condensation of sodium 3-oxo-3-(1-phenyl-1H-pyrazol-4-ylprop-1-en-1-olate (2 with several heterocyclic amines, cyanoacetamide, cyanothioacetamide, and 2-cyanoacetohydrazide gives pyrazolo[1,5-a]pyrimidines (5a–d, pyrido[2′,3′:3,4]pyrazolo[1,5-a]pyrimidine (9, benzo[4,5]imidazo[1,2-a]pyrimidine (10, [1,2,4]triazolo[1,5-a]pyrimidine (11, and pyridine derivatives (12–14. Also, thieno[2,3-b]pyridines (15–18 were synthesized via pyridinethione (13 with α-halo ketones and α-halo ester. Structures of the newly synthesized compounds were elucidated by elemental analysis, spectral data, alternative synthetic routes, and chemical transformation whenever possible.

  13. Simultaneous detection and semiquantification of DNA damage in normal and apoptotic cells: triple-immunofluorescent labeling using DAPI, antibodies, and TUNEL.

    Science.gov (United States)

    Agrawal, Anant; Godar, Dianne E

    2012-07-01

    We developed a triple-labeling immunofluorescence technique that simultaneously identifies total DNA (DAPI), DNA damage (antibodies), and dead cells [terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL)-positive cells] and a method that semiquantifies DNA damage in paraffin-embedded tissues. Using this technique in combination with our analysis method, scientists can now simultaneously detect and compare the relative amounts of DNA damage of almost any kind (except single-strand and double-strand breaks), using indirect fluorescent antibody labeling, in both normal and dying cells of different tissues. Simultaneous labeling of DNA damage and dead or TUNEL-positive cells can reduce processing costs and analysis time, and can lead to discoveries concerning how cells die from different DNA damages. We used increasing doses of UV (290 to 400 nm) radiation to create DNA damage in the form of cyclobutane pyrimidine dimers and 6-4 photoproducts that kill some of the cells in 3-dimensional tissue-engineered skin and vaginal samples. We describe a protocol that reliably detects and semiquantifies DNA damage in both normal and apoptotic cells. We show this triple-labeling immunofluorescence technique and analysis method yields linear UV dose response curves for damage to DNA bases that allows semiquantification of cyclobutane pyrimidine dimers and calculation of its repair rate (T=1 and 24 h), whereas TUNEL allows quantification of the number of apoptotic cells. Scientists can now create beautiful fluorescent pictures that simultaneously detect DNA damage in both normal and apoptotic cells to assess and semiquantify the damage to understand better how different insults lead to the cell's demise.

  14. Towards Multi Label Text Classification through Label Propagation

    Directory of Open Access Journals (Sweden)

    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. Radio labeling with pre-assigned frequencies

    NARCIS (Netherlands)

    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

  16. Radio labeling with pre-assigned frequencies

    NARCIS (Netherlands)

    Bodlaender, H.L.; Broersma, H.J.; Fomin, F.V.; Pyatkin, A.V.; Woeginer, 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 (RL) consists in determining a radio labeling that minimizes the maximum label that is used (the

  17. Radio labeling with pre-assigned frequencies

    NARCIS (Netherlands)

    Bodlaender, H.L.; Broersma, Haitze J.; Fomin, F.V.; Pyatkin, A.V.; Woeginger, Gerhard

    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

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

    Science.gov (United States)

    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.

  19. RutR is the uracil/thymine-sensing master regulator of a set of genes for synthesis and degradation of pyrimidines.

    Science.gov (United States)

    Shimada, Tomohiro; Hirao, Kiyo; Kori, Ayako; Yamamoto, Kaneyoshi; Ishihama, Akira

    2007-11-01

    Using the genomic SELEX, a total of six Escherichia coli DNA fragments have been identified, which formed complexes with transcription factor RutR. The RutR regulon was found to include a large number of genes encoding components for not only degradation of pyrimidines but also transport of glutamate, synthesis of glutamine, synthesis of pyrimidine nucleotides and arginine, and degradation of purines. DNase I footprinting indicated that RutR recognizes a palindromic sequence of TTGACCAnnTGGTCAA. The RutR box in P1 promoter of carAB encoding carbamoyl phosphate synthetase, a key enzyme of pyrimidine synthesis, overlaps with the PepA (CarP) repressor binding site, implying competition between RutR and PepA. Adding either uracil or thymine abolished RutR binding in vitro to the carAB P1 promoter. Accordingly, in the rutR-deletion mutant or in the presence of uracil, the activation in vivo of carAB P1 promoter was markedly reduced. Northern blot analysis of the RutR target genes indicated that RutR represses the Gad system genes involved in glutamate-dependent acid resistance and allantoin degradation. Altogether we propose that RutR is the pyrimidine sensor and the master regulator for a large set of the genes involved in the synthesis and degradation of pyrimidines.

  20. GEO label: The General Framework for Labeling and Certification

    Science.gov (United States)

    Bye, B. L.; McCallum, I.; Maso, J.

    2012-04-01

    The Group on Earth Observations (GEO) is coordinating efforts to build a Global Earth Observation System of Systems, or GEOSS. As part of a strategy to increase the involvement of the science and technology community in GEOSS, both as users and developers of GEOSS itself, GEO decided to develop a GEO label concept related to the scientific relevance, quality, acceptance and societal needs for services and data sets of GEOSS. The development of a GEO label is included in the GEO work plan and several projects address the challenges of developing a GEO label concept. Within the different projects developing the GEO label, various perspectives and approaches are being applied. In order to arrive at a generally accepted GEO label concept, a common understanding and basic knowledge of labeling is necessary. Assessment of quality of internationally standardized Earth observation data products implies possible certification. A general understanding of the framework for international standards and certification will also contribute to a more coherent discussion and more efficient development of a GEO label. We will describe the general labeling and certification framework emphasizing the relation to the three elements of the GEO label: quality, user acceptance and relevance. Based on a survey of international labels done by the EGIDA project, we have analyzed the legal framework and organization of labels and certification. We will discuss the frameworks for certification, user ratings, registration and analysis of user requirements. Quality assessment is a particular focus of the analysis and is based on the work done by the GeoViQua project. A GEO label will function both as a data distribution strategy and as a general management system for data. Through a label users can compare different data sets and get access to more information about the relevant data, including quality. A label will provide traceability of data both in the interest of users as well as data

  1. Sustainability labels on food products

    DEFF Research Database (Denmark)

    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......, human values as measured by the Schwartz value domains, and country differences. The results imply that sustainability labels currently do not play a major role in consumers’ food choices, and future use of these labels will depend on the extent to which consumers’ general concern about sustainability...

  2. 76 FR 75809 - Prior Label Approval System: Generic Label Approval

    Science.gov (United States)

    2011-12-05

    ... Food Standards and Labeling Policy Book; does not bear any special claims, such as quality claims... addition, deletion, or amendment of recipe suggestions for the product; j. Any change in punctuation; k... Policy Book, and questions and answers on various topics, such as irradiation and the labeling...

  3. Solvent control: dinuclear versus tetranuclear complexes of a bis-tetradentate pyrimidine-based ligand.

    Science.gov (United States)

    Gobeze, Worku A; Milway, Victoria A; Moubaraki, Boujemaa; Murray, Keith S; Brooker, Sally

    2012-08-28

    A new bis-tetradentate acyclic amine ligand L(Et) has been synthesized from 4,6-bis(aminomethyl)-2-phenylpyrimidine and 2-vinylpyridine. Dinuclear complexes, Mn(II)(2)L(Et)(MeCN)(H(2)O)(3)(ClO(4))(4) (1), Fe(II)(2)L(Et)(H(2)O)(4)(BF(4))(4) (2), Co(II)(2)L(Et)(H(2)O)(3)(MeCN)(2)(BF(4))(4) (3), Ni(II)(2)L(Et)(H(2)O)(4)(BF(4))(4) (4), Ni(II)(2)L(Et)(H(2)O)(4)(ClO(4))(4)·8H(2)O (4'), Cu(II)(2)L(Et)(BF(4))(4)·MeCN (5), Zn(II)(2)L(Et)(BF(4))(2)(BF(4))(2)·½MeCN (6), were obtained from 1 : 2 reactions of L(Et) and the appropriate metal salts in MeCN, whereas in MeOH tetranuclear complexes, Mn(II)(4)(L(Et))(2)(OH)(4)(ClO(4))(4) (7), Fe(II)(4)(L(Et))(2)(F)(4)(BF(4))(4)·5/2H(2)O (8), Co(II)(4)(L(Et))(2)(F)(4)(BF(4))(4)·3H(2)O (9), Ni(II)(4)(L(Et))(2)(F)(4)(BF(4))(4)·4H(2)O (10), Cu(II)(4)(L(Et))(2)(F)(4)(BF(4))(4)·3H(2)O (11) and Zn(II)(4)(L(Et))(2)(F)(4)(BF(4))(4) (12), result. Six complexes have been structurally characterized: in all cases each L(Et) is bis-tetradentate and provides a pyrimidine bridge between two metal centres. As originally anticipated, complexes 1, 4' and 6 are dinuclear, while 9, 10 and 12 are revealed to be tetranuclear, with two M(2)(L(Et))(4+) moieties bridged by two pairs of fluoride anions. Weak to moderate antiferromagnetic coupling between the metal centres is a feature of complexes 2, 3, 4, 8, 9 and 10. The dinuclear complexes 1-6 undergo multiple, mostly irreversible, redox processes. However, the pyrimidine-based dicopper(II) complex 5 undergoes a two electron quasi-reversible reduction, Cu(II)(2)→ Cu(I)(2), and this occurs at a more positive potential [E(m) = +0.11 V (E(pc) = -0.03 and E(pa) = +0.26 V) vs. 0.01 M AgNO(3)/Ag] than for either of the dicopper(II) complexes of the analogous pyrazine-based ligands.

  4. (3,5-Dimethylpyrazol-1-yl-[4-(1-phenyl-1H-pyrazolo[3,4-d]pyrimidin-4-ylaminophenyl]methanone

    Directory of Open Access Journals (Sweden)

    Rania B. Bakr

    2016-11-01

    Full Text Available In an attempt to enhance cytotoxic activity of pyrazolo[3,4-d]pyrimidine core, we synthesized (3,5-dimethylpyrazol-1-yl-[4-(1-phenyl-1H-pyrazolo[3,4-d]pyrimidin-4-ylaminophenyl]methanone (4 by reacting 4-(1-phenyl-1H-pyrazolo[3,4-d]pyrimidin-4-ylaminobenzohydrazide (3 with acetylacetone. Antiproliferative activity of this compound was screened against breast (MCF-7, colon (HCT-116, and liver (HEPG-2 cancer cell lines. The tested compound exhibited cytotoxic activity with IC50 = 5.00–32.52 μM. Moreover, inhibitory activity of this compound was evaluated against the epidermal growth factor receptor (EGFR, the fibroblast growth factor receptor (FGFR, the insulin receptor (IR, and the vascular endothelial growth factor receptor (VEGFR. This target compound showed potent inhibitory activity, especially against FGFR with IC50 = 5.18 μM.

  5. Poly[(μ(2)-2-amino-pyrimidine-κ(2)N(1):N(3))di-μ(2)-chlorido-mercury(II)].

    Science.gov (United States)

    Eshtiagh-Hosseini, Hossein; Yousefi, Zakieh; Janiak, Agnieszka

    2012-04-01

    The title compound, [HgCl(2)(C(4)H(5)N(3))](n), features a two-dimensional network parallel to (001) that is based on an Hg(II) atom octahedrally coordinated by four μ(2)-Cl atoms and two μ(2)-2-amino-pyrimidine (apym) ligands in trans positions, yielding a distorted HgCl(4)N(2) octa-hedron. The coordination network can be described as an uninodal 4-connected net with the sql topology. The Hg(II) ion lies on a site of -1 symmetry and the apym ligand lies on sites of m symmetry with the mirror plane perpendicular to the pyrimidine plane and passing through the NH(2) group N atom. This polymeric structure is stabilized by N-H⋯Cl hydrogen bonds and columnar π-π stacking of pyrimidine rings, with a centroid-centroid distance of 3.832 (2) Å.

  6. Discovery of pyrazolo[1,5-a]pyrimidine-based CHK1 inhibitors: A template-based approach-Part 2

    Energy Technology Data Exchange (ETDEWEB)

    Labroli, Marc; Paruch, Kamil; Dwyer, Michael P.; Alvarez, Carmen; Keertikar, Kartik; Poker, Cory; Rossman, Randall; Duca, Jose S.; Fischmann, Thierry O.; Madison, Vincent; Parry, David; Davis, Nicole; Seghezzi, Wolfgang; Wiswell, Derek; Guzi, Timothy J. [Merck

    2013-11-20

    Previous efforts by our group have established pyrazolo[1,5-a]pyrimidine as a viable core for the development of potent and selective CDK inhibitors. As part of an effort to utilize the pyrazolo[1,5-a]pyrimidine core as a template for the design and synthesis of potent and selective kinase inhibitors, we focused on a key regulator in the cell cycle progression, CHK1. Continued SAR development of the pyrazolo[1,5-a]pyrimidine core at the C5 and C6 positions, in conjunction with previously disclosed SAR at the C3 and C7 positions, led to the discovery of potent and selective CHK1 inhibitors.

  7. Hoogsteen-position pyrimidines promote the stability and function of the MALAT1 RNA triple helix.

    Science.gov (United States)

    Brown, Jessica A; Kinzig, Charles G; DeGregorio, Suzanne J; Steitz, Joan A

    2016-05-01

    Triple-stranded RNA was first deduced to form in vitro more than 50 years ago and has since been implicated in RNA catalysis, stability, and small molecule binding. Despite the emerging biological significance of RNA triple helices, it remains unclear how their nucleotide composition contributes to their thermodynamic stability and cellular function. To investigate these properties, we used in vitro RNA electrophoretic mobility shift assays (EMSAs) and in vivo intronless β-globin reporter assays to measure the relative contribution of 20 RNA base triples (N•A-U, N•G-C, N•C-G, N•U-A, and N•G-U) to triple-helical stability. These triples replaced a single internal U•A-U within the known structure of the triple-helical RNA stability element of human metastasis-associated lung adenocarcinoma transcript 1 (MALAT1), which contains 10 major-groove base triples. In addition to the canonical C•G-C triple, the noncanonical base triples U•G-C, U•G-U, C•C-G, and U•C-G exhibited at least 30% stability relative to the wild-type U•A-U base triple in both assays. Of these triples, only U•A-U, C•G-C, and U•G-C, when tested as four successive triples, formed stabilizing structures that allowed accumulation of the intronless β-globin reporter. Overall, we find that Hoogsteen-position pyrimidines support triple helix stability and function and that thermodynamic stability, based on EMSA results, is necessary but not sufficient for stabilization activity of the MALAT1 triple helix in cells. These results suggest that additional RNA triple helices containing noncanonical triples likely exist in nature.

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

  9. Spectroscopic analysis on the binding interaction of biologically active pyrimidine derivative with bovine serum albumin

    Directory of Open Access Journals (Sweden)

    Vishwas D. Suryawanshi

    2016-02-01

    Full Text Available A biologically active antibacterial reagent, 2–amino-6-hydroxy–4–(4-N, N-dimethylaminophenyl-pyrimidine-5-carbonitrile (AHDMAPPC, was synthesized. It was employed to investigate the binding interaction with the bovine serum albumin (BSA in detail using different spectroscopic methods. It exhibited antibacterial activity against Escherichia coli and Staphylococcus aureus which are common food poisoning bacteria. The experimental results showed that the fluorescence quenching of model carrier protein BSA by AHDMAPPC was due to static quenching. The site binding constants and number of binding sites (n≈1 were determined at three different temperatures based on fluorescence quenching results. The thermodynamic parameters, enthalpy change (ΔH, free energy (ΔG and entropy change (ΔS for the reaction were calculated to be 15.15 kJ/mol, –36.11 kJ/mol and 51.26 J/mol K according to van't Hoff equation, respectively. The results indicated that the reaction was an endothermic and spontaneous process, and hydrophobic interactions played a major role in the binding between drug and BSA. The distance between donor and acceptor is 2.79 nm according to Förster's theory. The alterations of the BSA secondary structure in the presence of AHDMAPPC were confirmed by UV–visible, synchronous fluorescence, circular dichroism (CD and three-dimensional fluorescence spectra. All these results indicated that AHDMAPPC can bind to BSA and be effectively transported and eliminated in the body. It can be a useful guideline for further drug design.

  10. Light-induced activation of class II cyclobutane pyrimidine dimer photolyases.

    Science.gov (United States)

    Okafuji, Asako; Biskup, Till; Hitomi, Kenichi; Getzoff, Elizabeth D; Kaiser, Gebhard; Batschauer, Alfred; Bacher, Adelbert; Hidema, Jun; Teranishi, Mika; Yamamoto, Kazuo; Schleicher, Erik; Weber, Stefan

    2010-05-04

    Light-induced activation of class II cyclobutane pyrimidine dimer (CPD) photolyases of Arabidopsis thaliana and Oryza sativa has been examined by UV/Vis and pulsed Davies-type electron-nuclear double resonance (ENDOR) spectroscopy, and the results compared with structure-known class I enzymes, CPD photolyase and (6-4) photolyase. By ENDOR spectroscopy, the local environment of the flavin adenine dinucleotide (FAD) cofactor is probed by virtue of proton hyperfine couplings that report on the electron-spin density at the positions of magnetic nuclei. Despite the amino-acid sequence dissimilarity as compared to class I enzymes, the results indicate similar binding motifs for FAD in the class II photolyases. Furthermore, the photoreduction kinetics starting from the FAD cofactor in the fully oxidized redox state, FAD(ox), have been probed by UV/Vis spectroscopy. In Escherichia coli (class I) CPD photolyase, light-induced generation of FADH from FAD(ox), and subsequently FADH(-) from FADH, proceeds in a step-wise fashion via a chain of tryptophan residues. These tryptophans are well conserved among the sequences and within all known structures of class I photolyases, but completely lacking from the equivalent positions of class II photolyase sequences. Nevertheless, class II photolyases show photoreduction kinetics similar to those of the class I enzymes. We propose that a different, but also effective, electron-transfer cascade is conserved among the class II photolyases. The existence of such electron transfer pathways is supported by the observation that the catalytically active fully reduced flavin state obtained by photoreduction is maintained even under oxidative conditions in all three classes of enzymes studied in this contribution.

  11. 2, 4-Diamino-6- hydroxy pyrimidine inhibits NSAIDs induced nitrosyl-complex EPR signals and ulcer in rat jejunum

    Science.gov (United States)

    Somasundaram, S; Simpson, R; Rafi, S; Shergill, JK; Bjarnason, I; Wrigglesworth, J

    2002-01-01

    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. PMID:11960558

  12. 2, 4-Diamino-6- hydroxy pyrimidine inhibits NSAIDs induced nitrosyl-complex EPR signals and ulcer in rat jejunum

    Directory of Open Access Journals (Sweden)

    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.

  13. Poly(alizarin red)/Graphene modified glassy carbon electrode for simultaneous determination of purine and pyrimidine

    Energy Technology Data Exchange (ETDEWEB)

    Ba Xi; Luo Liqiang [Department of Chemistry, Shanghai University, Shanghai 200444 (China); Ding Yaping, E-mail: wdingyp@sina.com [Department of Chemistry, Shanghai University, Shanghai 200444 (China); Zhang Zhen [Department of Chemistry, Shanghai University, Shanghai 200444 (China); Chu Yuliang [Instrumental Analysis and Research Center, Shanghai University, Shanghai 200444 (China); Wang Bijun; Ouyang Xiaoqian [Department of Chemistry, Shanghai University, Shanghai 200444 (China)

    2012-11-08

    Graphical abstract: DPVs of PAR/Graphene/GCE (a) and the bare GCE (c) in 0.1 M PBS containing 50.0 {mu}M G, 50.0 {mu}M A, 100.0 {mu}M T and 100.0 {mu}M C, (b) PAR/Graphene/GCE in 0.1 M PBS. Highlights: Black-Right-Pointing-Pointer The sensor exhibited well-separated peaks and low detection limit. Black-Right-Pointing-Pointer The sensor possesses high sensitivity and wide linear range. Black-Right-Pointing-Pointer The sensor was used for simultaneous detection of G, A, T and C successfully. Black-Right-Pointing-Pointer The sensor was applied in a fish sperm DNA sample with satisfactory results. Black-Right-Pointing-Pointer The proposed sensor has good stability and reproducibility. - Abstract: In this work, a poly(alizarin red)/Graphene composite film modified glassy carbon electrode (PAR/Graphene/GCE) was prepared for simultaneous determination of four DNA bases (guanine, adenine, thymine and cytosine) without any pretreatment. The morphology and interface property of PAR/Graphene films were examined by scanning electron microscopy and electrochemical impedance spectroscopy. The PAR/Graphene/GCE exhibited excellent electrocatalytic activity toward purine (guanine and adenine) and pyrimidine (thymine and cytosine) in 0.1 M phosphate buffer solution (pH 7.4). Under optimum conditions, differential pulse voltammetry was used to detect the oxidation of purine and pyrimidine. The results showed that PAR/Graphene/GCE exhibited well-separated peaks, low detection limit, high sensitivity and wide linear range for simultaneous detection of purine and pyrimidine. The proposed sensor also has good stability and reproducibility. Furthermore, the modified electrode was applied for the detection of DNA bases in a fish sperm DNA sample with satisfactory results.

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

    Directory of Open Access Journals (Sweden)

    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.

  15. An Efficient Synthesis of bi-Aryl Pyrimidine Heterocycles: Potential New Drug Candidates to Treat Alzheimer's Disease.

    Science.gov (United States)

    Rehman, Tanzeel Ur; Khan, Islam Ullah; Ashraf, Muhammad; Tarazi, Hamadeh; Riaz, Sadaf; Yar, Muhammad

    2017-02-21

    A series of 13 novel pyrimidine-based sulfonamides 6a-m were synthesized in short periods of time under microwave conditions in good to excellent yield (54-86%). The chemical structures of these heterocycles consist of a central pyrimidine ring having a phenyl group and pyrimidine groups with sulfonamide motifs. The enzyme inhibitory potential of these compounds was investigated against acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) because these enzymes play a crucial role in the treatment of Alzheimer's disease. As compared to the reference compound eserine (IC50  = 0.04 ± 0.0001 μM for AChE and IC50  = 0.85 ± 0.0001 μM for BChE), the IC50 values of the synthesized compounds ranged from 3.73 ± 0.61 μM to 57.36 ± 0.22 μM for AChE and 4.81 ± 0.16 μM to 111.61 ± 0.53 μM for BChE. Among these tested compounds, 6j having a -CH3 group was found to be the most potent one against both enzymes (AChE, IC50  = 3.73 ± 0.61 μM; BChE, IC50  = 4.81 ± 0.16 μM). Quantitative structure-activity relationship (QSAR) and molecular docking studies of the synthesized compounds were also performed.

  16. Quality Evaluation Model for Map Labeling

    Institute of Scientific and Technical Information of China (English)

    FAN Hong; ZHANG Zuxun; DU Daosheng

    2005-01-01

    This paper discusses and sums up the basic criterions of guaranteeing the labeling quality and abstracts the four basic factors including the conflict for a label with a label, overlay for label with the features, position's priority and the association for a label with its feature. By establishing the scoring system, a formalized four-factors quality evaluation model is constructed. Last, this paper introduces the experimental result of the quality evaluation model applied to the automatic map labeling system-MapLabel.

  17. Spectral and photophysical studies of inclusion complexes of 2-amino-4,6-dimethyl pyrimidine with beta-cyclodextrin.

    Science.gov (United States)

    El-Kemary, M A; El-Gezawy, H S; El-Baradie, H Y; Issa, R M

    2002-02-01

    The interaction of 2-amino-4,6-dimethyl pyrimidine (ADMP) with beta-cyclodextrin (beta-CD) has been studied by means of UV absorption, steady state and time resolved fluorescence techniques. Spectral characteristics, bandwidths and photophysical parameters indicating that ADMP experience two different environments in aqueous solutions: bulk water and 1:1 (ADMP:beta-CD) inclusion complexation. The size restriction of the upper rim of beta-CD partially include ADMP and prevent the possibility of formation of 1:2 complex. The effective polarity of the cyclodextrin cavity experienced by the induced ADMP is equivalent with the polarity of an 80:20 methanol-water mixture.

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

    Science.gov (United States)

    Wen, Yue-Zhong; Fang, Zhao-Hua; Liu, Wei-Ping

    2004-08-01

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

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

    Institute of Scientific and Technical Information of China (English)

    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 selective technology has been developed for the preparation of 3-(4,6-dimethoxy-pyrimidin-2-yloxy)-2-methyl-phenol (DPMP) from 2-methyl-benzene-1,3-diol in water as solvent. The isolated yield of DPMP is up to 86% in good selectivity. The product structure was characterized by conventional methods, 1H-NMR and MS. This technology belongs to the modern concept of environmentally friendly low wastes or non-wastes technology (LWNWT).

  20. 2-Anilino-4-(benzimidazol-2-yl)pyrimidines--a multikinase inhibitor scaffold with antiproliferative activity toward cancer cell lines.

    Science.gov (United States)

    Determann, Renate; Dreher, Jan; Baumann, Knut; Preu, Lutz; Jones, Peter G; Totzke, Frank; Schächtele, Christoph; Kubbutat, Michael H G; Kunick, Conrad

    2012-07-01

    2-Anilino-4-(benzimidazol-2-yl)-pyrimidines, synthesized by reaction of a readily available benzimidazole-substituted enaminone with suitable arylguanidines, were shown to inhibit four cancer-related protein kinases (Aurora B, PLK1, FAK, and VEGF-R2). The most potent derivative exhibited antiproliferative activity for several cancer cell lines of the NCI in vitro cell line panel in submicromolar concentrations. Both the anilinopyrimidine structure and the substitution pattern at the aniline ring appear to be important for the protein kinase inhibitory activity.

  1. Stretches of alternating pyrimidine/purines and purines are respectively linked with pathogenicity and growth temperature in prokaryotes

    DEFF Research Database (Denmark)

    Ussery, David; Bohlin, J; Hardy, SP

    2009-01-01

    -tracts are associated with phylum, AT content, oxygen requirement, growth temperature and halotolerance. All associations described were statistically significant with p factors......BACKGROUND: The genomic fractions of purine (RR) and alternating pyrimidine/purine (YR) stretches of 10 base pairs or more, have been linked to genomic AT content, the formation of different DNA helices, strand-biased gene distribution, DNA structure, and more. Although some of these factors...... 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...

  2. Multicomponent click synthesis of new 1,2,3-triazole derivatives of pyrimidine nucleobases: promising acidic corrosion inhibitors for steel.

    Science.gov (United States)

    González-Olvera, Rodrigo; Espinoza-Vázquez, Araceli; Negrón-Silva, Guillermo E; Palomar-Pardavé, Manuel E; Romero-Romo, Mario A; Santillan, Rosa

    2013-12-06

    A series of new mono-1,2,3-triazole derivatives of pyrimidine nucleobases were synthesized by one-pot copper(I)-catalyzed 1,3-dipolar cycloaddition reactions between N-1-propargyluracil and thymine, sodium azide and several benzyl halides. The desired heterocyclic compounds were obtained in good yields and characterized by NMR, IR, and high resolution mass spectrometry. These compounds were investigated as corrosion inhibitors for steel in 1 M HCl solution, using electrochemical impedance spectroscopy (EIS) technique. The results indicate that these heterocyclic compounds are promising acidic corrosion inhibitors for steel.

  3. Design and synthesis of novel 1,2,3-triazole-pyrimidine-urea hybrids as potential anticancer agents.

    Science.gov (United States)

    Ma, Li-Ying; Wang, Bo; Pang, Lu-Ping; Zhang, Miao; Wang, Sai-Qi; Zheng, Yi-Chao; Shao, Kun-Peng; Xue, Deng-Qi; Liu, Hong-Min

    2015-03-01

    A series of novel 1,2,3-triazole-pyrimidine-urea hybrids were designed, synthesized and evaluated for anticancer activity against four selected cancer cell lines (MGC-803, EC-109, MCF-7 and B16-F10). Majority of the synthesized compounds exhibited moderate to potent activity against all the cancer cell lines assayed. Particularly, compounds 26, 30 and 38 exhibited excellent growth inhibition against B16-F10 with IC50 values of 32nM, 35nM and 42nM, respectively. Flow cytometry analysis demonstrated that compound 26 induced the cellular apoptosis in a concentration-dependent manner.

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

    Science.gov (United States)

    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.

  5. The growth rate of pyrimidine auxotrophic mutants of Lactococcus lactis MG1363 is reduced in the presence of exogenous aspartate

    DEFF Research Database (Denmark)

    Hansen, Steen Lyders Lerche; Martinussen, Jan

    1998-01-01

    encoding enzymes in the distal part of the pyrimidine biosynthetic pathway of L. lactis MG1363, results in reduction of the growth rate if exogenous aspartate is supplied to the growth medium. This observation can be explained by an increased accumulation of a toxic intermediate, most likely carbamoyl......Nucleotide metabolism is important for all cells as supplier of building blocks for the synthesis of nucleic acids and coenzymes. Furthermore, they act as intracellular energy carriers and allosteric effectors in a large number of enzymatic reactions. Nucleotides can either be made de novo or from...

  6. Aminopyrazolo[1,5-a]pyrimidines as potential inhibitors of Mycobacterium tuberculosis: Structure activity relationships and ADME characterization.

    Science.gov (United States)

    Soares de Melo, Candice; Candice, Soares de Melo; Feng, Tzu-Shean; van der Westhuyzen, Renier; Gessner, Richard K; Street, Leslie J; Morgans, Garreth L; Warner, Digby F; Moosa, Atica; Naran, Krupa; Lawrence, Nina; Boshoff, Helena I M; Barry, Clifton E; Harris, C John; Gordon, Richard; Chibale, Kelly

    2015-11-15

    Whole-cell high-throughput screening of a diverse SoftFocus library against Mycobacterium tuberculosis (Mtb) generated a novel aminopyrazolo[1,5-a]pyrimidine hit series. The synthesis and structure activity relationship studies identified compounds with potent antimycobacterial activity. The SAR of over 140 compounds shows that the 2-pyridylmethylamine moiety at the C-7 position of the pyrazolopyrimidine scaffold was important for Mtb activity, whereas the C-3 position offered a higher degree of flexibility. The series was also profiled for in vitro cytotoxicity and microsomal metabolic stability as well as physicochemical properties. Consequently liabilities to be addressed in a future lead optimization campaign have been identified.

  7. Multicomponent Click Synthesis of New 1,2,3-Triazole Derivatives of Pyrimidine Nucleobases: Promising Acidic Corrosion Inhibitors for Steel

    Directory of Open Access Journals (Sweden)

    Rodrigo González-Olvera

    2013-12-01

    Full Text Available A series of new mono-1,2,3-triazole derivatives of pyrimidine nucleobases were synthesized by one-pot copper(I-catalyzed 1,3-dipolar cycloaddition reactions between N-1-propargyluracil and thymine, sodium azide and several benzyl halides. The desired heterocyclic compounds were obtained in good yields and characterized by NMR, IR, and high resolution mass spectrometry. These compounds were investigated as corrosion inhibitors for steel in 1 M HCl solution, using electrochemical impedance spectroscopy (EIS technique. The results indicate that these heterocyclic compounds are promising acidic corrosion inhibitors for steel.

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

    Institute of Scientific and Technical Information of China (English)

    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

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

    Institute of Scientific and Technical Information of China (English)

    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).

  10. Synthesis and biological evaluation of 4,6-diaryl substituted-4,5-dihydro-2-amino pyrimidines

    Directory of Open Access Journals (Sweden)

    Venkatesan J

    2007-01-01

    Full Text Available 4,6-Diaryl substituted-4,5-dihydro-2-amino pyrimidines have been synthesized by the reaction of chalcones with guanidine nitrate. Their chemical structures have been confirmed by means of IR and NMR data and by elemental analysis. The compounds were screened for antibacterial activity against 16 gram-positive bacterial strains in minimum inhibitory concentration. The minimum inhibitory concentration of the compound II has found to be better than the reference standards taken for the antibacterial screening. Sulphamethoxazole and trimethoprim were taken as reference standards.

  11. Non-hinge-binding pyrazolo[1,5-a]pyrimidines as potent B-Raf kinase inhibitors

    Energy Technology Data Exchange (ETDEWEB)

    Berger, Dan M.; Torres, Nancy; Dutia, Minu; Powell, Dennis; Ciszewski, Greg; Gopalsamy, Ariamala; Levin, Jeremy I.; Kim, Kyung-Hee; Xu, Weixin; Wilhelm, James; Hu, YongBo; Collins, Karen; Feldberg, Larry; Kim, Steven; Frommer, Eileen; Wojciechowicz, Donald; Mallon, Robert; (Wyeth)

    2010-11-19

    As part of our research effort to discover B-Raf kinase inhibitors, we prepared a series of C-3 substituted N-(3-(pyrazolo[1,5-a]pyrimidin-7-yl)phenyl)-3-(trifluoromethyl)benzamides. X-ray crystallography studies revealed that one of the more potent inhibitors (10n) bound to B-Raf kinase without forming a hinge-binding hydrogen bond. With basic amine residues appended to C-3 aryl residues, cellular activity and solubility were enhanced over previously described compounds of this class.

  12. Unconventional hydrogen bonding to organic ions in the gas phase: stepwise association of hydrogen cyanide with the pyridine and pyrimidine radical cations and protonated pyridine.

    Science.gov (United States)

    Hamid, Ahmed M; El-Shall, M Samy; Hilal, Rifaat; Elroby, Shaaban; Aziz, Saadullah G

    2014-08-07

    Equilibrium thermochemical measurements using the ion mobility drift cell technique have been utilized to investigate the binding energies and entropy changes for the stepwise association of HCN molecules with the pyridine and pyrimidine radical cations forming the C5H5N(+·)(HCN)n and C4H4N2 (+·)(HCN)n clusters, respectively, with n = 1-4. For comparison, the binding of 1-4 HCN molecules to the protonated pyridine C5H5NH(+)(HCN)n has also been investigated. The binding energies of HCN to the pyridine and pyrimidine radical cations are nearly equal (11.4 and 12.0 kcal/mol, respectively) but weaker than the HCN binding to the protonated pyridine (14.0 kcal/mol). The pyridine and pyrimidine radical cations form unconventional carbon-based ionic hydrogen bonds with HCN (CH(δ+)⋯NCH). Protonated pyridine forms a stronger ionic hydrogen bond with HCN (NH(+)⋯NCH) which can be extended to a linear chain with the clustering of additional HCN molecules (NH(+)⋯NCH··NCH⋯NCH) leading to a rapid decrease in the bond strength as the length of the chain increases. The lowest energy structures of the pyridine and pyrimidine radical cation clusters containing 3-4 HCN molecules show a strong tendency for the internal solvation of the radical cation by the HCN molecules where bifurcated structures involving multiple hydrogen bonding sites with the ring hydrogen atoms are formed. The unconventional H-bonds (CH(δ+)⋯NCH) formed between the pyridine or the pyrimidine radical cations and HCN molecules (11-12 kcal/mol) are stronger than the similar (CH(δ+)⋯NCH) bonds formed between the benzene radical cation and HCN molecules (9 kcal/mol) indicating that the CH(δ+) centers in the pyridine and pyrimidine radical cations have more effective charges than in the benzene radical cation.

  13. A better carbon footprint label

    DEFF Research Database (Denmark)

    Thøgersen, John; Nielsen, Kristian S.

    2016-01-01

    , participants saw the original Carbon Trust label and in the other condition they saw the same label, but with traffic light colors added to communicate the product’s relative performance in terms of carbon footprint. All included attributes were found to have a significant impact on consumer choices...

  14. Nutrition Marketing on Food Labels

    Science.gov (United States)

    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. Nutrition Marketing on Food Labels

    Science.gov (United States)

    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…

  16. Distance labeling schemes for trees

    DEFF Research Database (Denmark)

    Alstrup, Stephen; Gørtz, Inge Li; Bistrup Halvorsen, Esben

    2016-01-01

    variants such as, for example, small distances in trees [Alstrup et al., SODA, 2003]. We improve the known upper and lower bounds of exact distance labeling by showing that 1/4 log2(n) bits are needed and that 1/2 log2(n) bits are sufficient. We also give (1 + ε)-stretch labeling schemes using Theta...

  17. One-pot synthesis of pyrido[2,3-d]pyrimidine derivatives using sulfonic acid functionalized SBA-15 and the study on their antimicrobial activities

    Directory of Open Access Journals (Sweden)

    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.

  18. Regiospecific one-pot synthesis of pyrimido[4,5-d]pyrimidine derivatives in the solid state under microwave irradiations.

    Science.gov (United States)

    Prajapati, Dipak; Gohain, Mukut; Thakur, Ashim J

    2006-07-01

    Electron rich 6-[(dimethylamino)methylene]amino uracil 1, undergoes [4+2] cycloaddition reactions with various in situ generated glyoxylate imine and imine oxides 6 to provide novel pyrimido[4,5-d]pyrimidine derivatives of biological significance, after elimination of dimethylamine from the (1:1) cycloadducts and oxidative aromatisation. This procedure provides a convenient method for the direct synthesis of pyrimido[4,5-d]pyrimidines in excellent yields when carried out in the solid state and under microwave irradiations.

  19. False positives and false negatives measure less than 0.001% in labeling ssDNA with osmium tetroxide 2,2’-bipyridine

    Directory of Open Access Journals (Sweden)

    Anastassia Kanavarioti

    2016-10-01

    Full Text Available Osmium tetroxide 2,2’-bipyridine (OsBp is known to react with pyrimidines in ssDNA and preferentially label deoxythymine (T over deoxycytosine (C. The product, osmylated DNA, was proposed as a surrogate for nanopore-based DNA sequencing due to OsBp’s “perfect” label attributes. Osmylated deoxyoligos translocate unassisted and measurably slow via sub-2 nm SiN solid-state nanopores, as well as via the alpha-hemolysin (α-HL pore. Both nanopores discriminate clearly between osmylated and intact nucleobase; α-HL was also shown to discriminate between osmylated T and osmylated C. Experiments presented here confirm that the kinetics of osmylation are comparable for short oligos and long ssDNA and show that pyrimidine osmylation is practically complete in two hours at room temperature with less than 15 mM OsBp. Under the proposed labeling conditions: deoxyoligo backbone degradation measures less than 1/1,000,000; false positives such as osmylated deoxyadenine (A and osmylated deoxyguanine (G measure less than 1/100,000; false negatives, i.e., unosmylated C measure less than 1/10,000; and unosmylated T must measure substantially lower than 1/10,000 due to the 27-fold higher reactivity of T compared to C. However, osmylated C undergoes degradation that amounts to about 1–2% for the duration of the labeling protocol. This degradation may be further characterized, possibly suppressed, and the properties of the degradation products via nanopore translocation can be evaluated to assure base calling quality in a DNA sequencing effort.

  20. 16 CFR 460.12 - Labels.

    Science.gov (United States)

    2010-01-01

    ... 16 Commercial Practices 1 2010-01-01 2010-01-01 false Labels. 460.12 Section 460.12 Commercial Practices FEDERAL TRADE COMMISSION TRADE REGULATION RULES LABELING AND ADVERTISING OF HOME INSULATION § 460.12 Labels. If you are a manufacturer, you must label all packages of your insulation. The labels...

  1. 21 CFR 201.71 - Magnesium labeling.

    Science.gov (United States)

    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...

  2. 21 CFR 610.60 - Container label.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 7 2010-04-01 2010-04-01 false Container label. 610.60 Section 610.60 Food and... GENERAL BIOLOGICAL PRODUCTS STANDARDS Labeling Standards § 610.60 Container label. (a) Full label. The following items shall appear on the label affixed to each container of a product capable of bearing a...

  3. Labeled Cocaine Analogs

    Science.gov (United States)

    Goodman, Mark M.; Shi, Bing Zhi; Keil, Robert N.

    1999-01-26

    Novel compounds having the structure: ##STR1## where X in .beta. configuration is phenyl, naphthyl; 2,3 or 4-iodophenyl; 2,3 or 4-(trimethylsilyl)phenyl; 3,4,5 or 6-iodonaphthyl; 3,4,5 or 6-(trimethylsilyl)naphthyl; 2,3 or 4-(trialkylstannyl)phenyl; or 3,4,5 or 6-(trialkylstannyl)naphthyl Y in .beta. configuration is Y.sub.1 or Y.sub.2, where Y.sub.1 is 2-fluoroethoxy, 3-fluoropropoxy, 4-fluorobutoxy, 2-fluorocyclopropoxy, 2 or 3-fluorocyclobutoxy, R,S 1'-fluoroisopropoxy, R 1'-fluoroisopropoxy, S 1'-fluoroisopropoxy, 1',3'-difluoroisopropoxy, R,S 1'-fluoroisobutoxy, R 1'-fluoroisobutoxy, S 1'-fluoroisobutoxy, R,S 4'-fluoroisobutoxy, R 4'-fluoroisobutoxy, S 4'-fluoroisobutoxy, or 1',1'-di(fluoromethyl)isobutoxy, and Y.sub.2 is 2-methanesulfonyloxy ethoxy, 3-methanesulfonyloxy propoxy, 4-methanesulfonyloxy butoxy, 2-methanesulfonyloxy cyclopropoxy, 2 or 3-methanesulfonyloxy cyclobutoxy, 1'methanesulfonyloxy isopropoxy, 1'-fluoro, 3'-methanesulfonyloxy isopropoxy, 1'-methanesulfonyloxy, 3'-fluoro isopropoxy, 1'-methanesulfonyloxy isobutoxy, or 4'-methanesulfonyloxy isobutoxy bind dopamine transporter protein and can be labeled with .sup.18 F or .sup.123 I for imaging.

  4. Synthesis Of Labeled Metabolites

    Science.gov (United States)

    Martinez, Rodolfo A.; Silks, III, Louis A.; Unkefer, Clifford J.; Atcher, Robert

    2004-03-23

    The present invention is directed to labeled compounds, for example, isotopically enriched mustard gas metabolites including: [1,1',2,2'-.sup.13 C.sub.4 ]ethane, 1,1'-sulfonylbis[2-(methylthio); [1,1',2,2'-.sup.13 C.sub.4 ]ethane, 1-[[2-(methylsulfinyl)ethyl]sulfonyl]-2-(methylthio); [1,1',2,2'-.sup.13 C.sub.4 ]ethane, 1,1'-sulfonylbis[2-(methylsulfinyl)]; and, 2,2'-sulfinylbis([1,2-.sup.13 C.sub.2 ]ethanol of the general formula ##STR1## where Q.sup.1 is selected from the group consisting of sulfide (--S--), sulfone (--S(O)--), sulfoxide (--S(O.sub.2)--) and oxide (--O--), at least one C* is .sup.13 C, X is selected from the group consisting of hydrogen and deuterium, and Z is selected from the group consisting of hydroxide (--OH), and --Q.sup.2 --R where Q.sup.2 is selected from the group consisting of sulfide (--S--), sulfone(--S(O)--), sulfoxide (--S(O.sub.2)--) and oxide (--O--), and R is selected from the group consisting of hydrogen, a C.sub.1 to C.sub.4 lower alkyl, and amino acid moieties, with the proviso that when Z is a hydroxide and Q.sup.1 is a sulfide, then at least one X is deuterium.

  5. Synthesis, characterization and spectrochemical studies on a few binuclear -oxo molybdenum(V) complexes of pyrimidine derived Schiff base ligands

    Indian Academy of Sciences (India)

    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.

  6. Erythroid pyrimidine 5'-nucleotidase: cloning, developmental expression, and regulation by cAMP and in vivo hypoxia.

    Science.gov (United States)

    Mass, Markus; Simo, Erika; Dragon, Stefanie

    2003-12-01

    A characteristic process of terminal erythroid differentiation is the degradation of ribosomal RNA into mononucleotides. The pyrimidine mononucleotides can be dephosphorylated by pyrimidine 5'-nucleotidase (P5N-I). In humans, a lack of this enzyme causes hemolytic anemia with ribosomal structures and trinucleotides retained in the red blood cells (RBCs). Although the protein/nucleotide sequence of P5N-I is known in mammals, the onset and regulation of P5N-I during erythroid maturation is unknown. However, in circulating chicken embryonic RBCs, the enzyme is induced together with carbonic anhydrase (CAII) and 2,3-bisphosphoglycerate (2,3-BPG) by norepinephrine (NE) and adenosine, which are released by the embryo under hypoxic conditions. Here, we present the chicken P5N-I sequence and the gene expression of P5N-I during RBC maturation; the profile of gene expression follows the enzyme activity with a rise between days 13 and 16 of embryonic development. The p5n-I expression is induced (1) in definitive but not primitive RBCs by stimulation of beta-adrenergic/adenosine receptors, and (2) in definitive RBCs by hypoxic incubation of the chicken embryo. Since embryonic RBCs increase their hemoglobin-oxygen affinity by degradation of nucleotides such as uridine triphosphate (UTP) and cytidine triphosphate (CTP), the induction of p5n-I expression can be seen as an adaptive response to hypoxia.

  7. Synthesis of New Visnagen and Khellin Furochromone Pyrimidine Derivatives and Their Anti-Inflammatory and Analgesic Activity

    Directory of Open Access Journals (Sweden)

    Ameen Ali Abu-Hashem

    2011-02-01

    Full Text Available 6-[(4-Methoxy/4,9-dimethoxy-7-methylfurochromen-5-ylideneamino]-2-thioxo-2,3-dihydropyrimidin-4-ones 1a,b were prepared by reaction of 6-amino-2-thiouracil with visnagen or khellin, respectively. Reaction of 1a,b with methyl iodide afforded furochromenylideneaminomethylsulfanylpyrimidin-4-ones 2a,b. Compounds 2a,b were reacted with secondary aliphatic amines to give the corresponding furochromen-ylideneamino-2-substituted pyrimidin-4-ones 3a–d. Reaction of 3a–d with phosphorus oxychloride yielded 6-chlorofurochromenylidenepyrimidinamines 4a–d, which were reacted with secondary amines to afford furochromenylideneamino-2,6-disubstituted pyrimidin-4-ones 5a–d. In addition, reaction of 5a–d with 3-chloropentane-2,4-dione gave 3-chloro-furochromenylpyrimidopyrimidines 6a–d. The latter were reacted with piperazine and morpholine to give 1-(furochromenyl-pyrimidopyrimidine-3,6,8-triylpiperazines or -3,6,8-triylmorpholines 7a–d. The chemical structures of the newly synthesized compound ware characterized by IR, 1H-NMR, 13C-NMR and mass spectral analysis. These compounds were also screened for their analgesic and anti-inflammatory activities. Some of them, particularly 3–7, exhibited promising activities.

  8. Crystal structures of two 6-(2-hydroxybenzoyl-5H-thiazolo[3,2-a]pyrimidin-5-ones

    Directory of Open Access Journals (Sweden)

    Ligia R. Gomes

    2015-07-01

    Full Text Available The title compounds, 6-(2-hydroxybenzyl-5H-thiazolo[3,2-a]pyrimidin-5-one, C13H8N2O3S, (1, and 6-(2-hydroxybenzyl-3-methyl-5H-thiazolo[3,2-a]pyrimidin-5-one, C14H10N2O3S, (2, were synthesized when a chromone-3-carboxylic acid, activated with (benzotriazol-1-yloxytripyrrolidinylphosphonium hexafluoridophosphate (PyBOP, was reacted with a primary heteromamine. Instead of the expected amidation, the unusual title thiazolopyrimidine-5-one derivatives were obtained serendipitously and a mechanism of formation is proposed. Both compounds present an intramolecular O—H...O hydrogen bond, which generates an S(6 ring. The dihedral angles between the heterocyclic moiety and the 2-hydroxybenzoyl ring are 55.22 (5 and 46.83 (6° for (1 and (2, respectively. In the crystals, the molecules are linked by weak C—H...O hydrogen bonds and π–π stacking interactions.

  9. 6-(3,5-Dimethylbenzyl-5-ethyl-1-[(2-phenylethoxymethyl]pyrimidine-2,4(1H,3Hdione

    Directory of Open Access Journals (Sweden)

    Nasser R. El-Brollosy

    2012-04-01

    Full Text Available In the title pyrimidine derivative, C24H28N2O3, the uracil unit is essentially planar with an r.m.s. deviation of 0.0054 (1 Å for the eight non-H atoms. The pyrimidine ring is tilted by a dihedral angle of 77.08 (7° with respect to the aromatic ring of the 3,5-dimethylbenzyl substituent, whereas it is nearly parallel to the benzene ring of the phenethoxymethyl unit, with a dihedral angle of 8.17 (8°. An intramolecular C—H...O hydrogen bond generates an S(6 ring motif. In the crystal, molecules are linked by a pair of amide–uracil N—H...O hydrogen bonds into an inversion R22(8 dimer. These dimers are stacked along the b axis through π–π interactions with a centroid–centroid distance of 3.9517 (8 Å. Weak C—H...π interactions are also present.

  10. TD-DFT investigation of the magnetic circular dichroism spectra of some purine and pyrimidine bases of nucleic acids.

    Science.gov (United States)

    Fahleson, Tobias; Kauczor, Joanna; Norman, Patrick; Santoro, Fabrizio; Improta, Roberto; Coriani, Sonia

    2015-05-28

    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 alter the qualitative shape of the spectra. The bands are dominated by the bright π → π* transitions, and our calculations in solution nicely reproduce their energy differences, improving the estimates obtained in the gas phase. Shoulders are predicted for purine and uracil due to n → π* excitations, but they are too weak to be observed in the experiment.

  11. Algorithms for Labeling Focus Regions.

    Science.gov (United States)

    Fink, M; Haunert, Jan-Henrik; Schulz, A; Spoerhase, J; Wolff, A

    2012-12-01

    In this paper, we investigate the problem of labeling point sites in focus regions of maps or diagrams. This problem occurs, for example, when the user of a mapping service wants to see the names of restaurants or other POIs in a crowded downtown area but keep the overview over a larger area. Our approach is to place the labels at the boundary of the focus region and connect each site with its label by a linear connection, which is called a leader. In this way, we move labels from the focus region to the less valuable context region surrounding it. In order to make the leader layout well readable, we present algorithms that rule out crossings between leaders and optimize other characteristics such as total leader length and distance between labels. This yields a new variant of the boundary labeling problem, which has been studied in the literature. Other than in traditional boundary labeling, where leaders are usually schematized polylines, we focus on leaders that are either straight-line segments or Bezier curves. Further, we present algorithms that, given the sites, find a position of the focus region that optimizes the above characteristics. We also consider a variant of the problem where we have more sites than space for labels. In this situation, we assume that the sites are prioritized by the user. Alternatively, we take a new facility-location perspective which yields a clustering of the sites. We label one representative of each cluster. If the user wishes, we apply our approach to the sites within a cluster, giving details on demand.

  12. How to Read a Nutrition Facts Label

    Medline Plus

    Full Text Available ... las etiquetas de datos nutricionales (video) Most packaged foods come with a Nutrition Facts label. These labels ... Watch this video for tips on figuring out food labels so you can make healthy choices. For ...

  13. How to Read a Nutrition Facts Label

    Medline Plus

    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 ...

  14. How to Read a Nutrition Facts Label

    Medline Plus

    Full Text Available ... las etiquetas de datos nutricionales (video) Most packaged foods come with a Nutrition Facts label. These labels ... Watch this video for tips on figuring out food labels so you can make healthy choices. For ...

  15. Association of poly-purine/poly-pyrimidine sequences with meiotic recombination hot spots

    Directory of Open Access Journals (Sweden)

    Pitt Joel PW

    2006-07-01

    Full Text Available Abstract Background Meiotic recombination events have been found to concentrate in 1–2.5 kilo base regions, but these recombination hot spots do not share a consensus sequence and why they occur at specific sites is not fully understood. Some previous evidence suggests that poly-purine/poly-pyrimidine (poly-pu/py tracts (PPTs, a class of sequence with distinctive biochemical properties, could be involved in recombination, but no general association of PPTs with meiotic recombination hot spots has previously been reported. Results We used computational methods to investigate in detail the relationship between PPTs and hot spots. We show statistical associations of PPT frequency with hot spots of meiotic recombination initiating lesions, double-strand breaks, in the genome of the yeast S. cerevisiae and with experimentally well characterized human meiotic recombination hot spots. Supporting a possible role of poly-pu/py-rich sequences in hot spot recombination, we also found that all three single nucleotide polymorphisms previously shown to be associated with human hot spot activity changes occur within sequence contexts of 14 bp or longer that are 85% or more poly-pu/py and at least 70% G/C. These polymorphisms are all close to the hot spot mid points. Comparing the sequences of experimentally characterized human hot spots with the orthologous regions of the chimpanzee genome previously shown not to contain hot spots, we found that in all five cases in which comparisons for the hot spot central regions are possible with publicly available sequence data, there are differences near the human hot spot mid points within sequences 14 bp or longer consisting of more than 80% poly-pu/py and at least 50% G/C. Conclusion Our results, along with previous evidence for the unique biochemical properties and recombination-stimulating potential of poly-pu/py-rich sequences, suggest that the possible functional involvement of this type of sequence in meiotic

  16. Labelling of benzocaine with tritium

    Energy Technology Data Exchange (ETDEWEB)

    Malik, Sohail (Washington Univ., Seattle, WA (United States))

    1994-10-01

    A convenient method is described to label a local anesthetic, benzocaine, with tritium. The bromoester of para-aminobenzoic acid (PABA) was prepared from para-nitrotoluene and was reduced with tritium. The generation of isotopic hydrogen and labelling of benzocaine was achieved in one-step. A mixture of sodium borohydride (NaB[sup 3]H[sub 4]) with cobalt (II) chloride was used to generate tritium gas. 5% Pd/C was used as a catalyst. This constitutes the first report of tritium labelled benzocaine. (author).

  17. New labels for radiation therapy

    Energy Technology Data Exchange (ETDEWEB)

    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.).

  18. General Compact Labeling Schemes for Dynamic Trees

    OpenAIRE

    2006-01-01

    Let $F$ be a function on pairs of vertices. An {\\em $F$- labeling scheme} is composed of a {\\em marker} algorithm for labeling the vertices of a graph with short labels, coupled with a {\\em decoder} algorithm allowing one to compute $F(u,v)$ of any two vertices $u$ and $v$ directly from their labels. As applications for labeling schemes concern mainly large and dynamically changing networks, it is of interest to study {\\em distributed dynamic} labeling schemes. This paper investigates labelin...

  19. De novo pyrimidine nucleotide synthesis mainly occurs outside of plastids, but a previously undiscovered nucleobase importer provides substrates for the essential salvage pathway in Arabidopsis.

    Science.gov (United States)

    Witz, Sandra; Jung, Benjamin; Fürst, Sarah; Möhlmann, Torsten

    2012-04-01

    Nucleotide de novo synthesis is highly conserved among organisms and represents an essential biochemical pathway. In plants, the two initial enzymatic reactions of de novo pyrimidine synthesis occur in the plastids. By use of green fluorescent protein fusions, clear support is provided for a localization of the remaining reactions in the cytosol and mitochondria. This implies that carbamoyl aspartate, an intermediate of this pathway, must be exported and precursors of pyrimidine salvage (i.e., nucleobases or nucleosides) are imported into plastids. A corresponding uracil transport activity could be measured in intact plastids isolated from cauliflower (Brassica oleracea) buds. PLUTO (for plastidic nucleobase transporter) was identified as a member of the Nucleobase:Cation-Symporter1 protein family from Arabidopsis thaliana, capable of transporting purine and pyrimidine nucleobases. A PLUTO green fluorescent protein fusion was shown to reside in the plastid envelope after expression in Arabidopsis protoplasts. Heterologous expression of PLUTO in an Escherichia coli mutant lacking the bacterial uracil permease uraA allowed a detailed biochemical characterization. PLUTO transports uracil, adenine, and guanine with apparent affinities of 16.4, 0.4, and 6.3 μM, respectively. Transport was markedly inhibited by low concentrations of a proton uncoupler, indicating that PLUTO functions as a proton-substrate symporter. Thus, a protein for the absolutely required import of pyrimidine nucleobases into plastids was identified.

  20. 1-(2-(2,2,2-trifluoroethoxy)ethyl-1H-pyrazolo[4,3-d]pyrimidines as potent phosphodiesterase 5 (PDE5) inhibitors.

    Science.gov (United States)

    Tollefson, Michael B; Acker, Brad A; Jacobsen, E J; Hughes, Robert O; Walker, John K; Fox, David N A; Palmer, Michael J; Freeman, Sandra K; Yu, Ying; Bond, Brian R

    2010-05-15

    1H-Pyrazolo[4,3-d]pyrimidines were previously disclosed as a potent second generation class of phosphodiesterase 5 (PDE5) inhibitors. This work explores the advancement of more selective and potent PDE5 inhibitors resulting from the substitution of 2-(2,2,2-trifluoroethoxy)ethyl at the 1 position in the so-called alkoxy pocket.

  1. An efficient route for annulation of pyrimidines to steroids and non-steroids via a base catalyzed one-pot three component reaction.

    Science.gov (United States)

    Saikia, Pallabi; Gogoi, Shyamalee; Gogoi, Sanjib; Boruah, Romesh C

    2014-10-01

    A facile strategy for the synthesis of steroidal A- and D-ring fused pyrimidines has been accomplished in high yields via a one-pot reaction of steroidal ketones, aromatic aldehydes and amidine derivatives in presence of potassium tert-butoxide in refluxing ethanol. The generality of the reaction was also extended to non-steroidal ketones.

  2. A Selective Synthesis of 2-Alkylamino-5, 6, 7, 8-tetrahydro benzothieno[2, 3-d]pyrimidin-4(3H)-ones

    Institute of Scientific and Technical Information of China (English)

    Ming Wu DING; Rui Jun XU; Jing XU; Yun Feng CHEN

    2005-01-01

    2-Alkylamino-5, 6, 7, 8-tetrahydrobenzothieno [2, 3-d] pyrimidin-4(3H)-ones 7 were synthesized by a new selective synthetic method, which includes aza-Wittig reaction of iminophosphorane 4 with aromatic isocynate to give carbodiimide 5 and subsequent reaction of 5 with various aliphatic primary amine in the presence of EtO-Na+.

  3. Synthesis of novel pyrido[3,2-e][1,2,4]triazolo[1,5-c]pyrimidine derivatives: potent and selective adenosine A3 receptor antagonists.

    Science.gov (United States)

    Banda, Veeraswamy; Chandrasekaran, Balakumar; Köse, Meryem; Vielmuth, Christin; Müller, Christa E; Chavva, Kurumurthy; Gautham, Santhosh Kumar; Pillalamarri, Sambasivarao; Mylavaram, Raghuprasad; Akkinepally, Raghuramarao; Pamulaparthy, Shanthanrao; Banda, Narsaiah

    2013-10-01

    A series of novel pyrido[3,2-e][1,2,4]triazolo[1,5-c]pyrimidine derivatives 5 was prepared from 2-amino-3-cyano-4-trifluoromethyl-6-phenylpyridine 1 in two steps via formation of iminoether 3 followed by reaction with different aroylhydrazides 4. Representative products 5 were evaluated for their affinity towards all four subtypes of human adenosine receptors. Compounds 2-(3-fluorophenyl)-8-phenyl-10-(trifluoromethyl)pyrido[3,2-e][1,2,4]triazolo[1,5-c]pyrimidine (5b), 2-(furan-2-yl)-8-phenyl-10-(trifluoromethyl)pyrido[3,2-e][1,2,4]triazolo[1,5-c]pyrimidine (5d), and 2-(furan-2-yl)-5-methyl-8-phenyl-10-(trifluoromethyl)pyrido[3,2-e][1,2,4]triazolo[1,5-c]pyrimidine (5j) showed high affinity for the A3 receptors, with Ki values of 8.1, 10.4, and 12.1 nM, respectively, and were >1000-fold selective versus all other adenosine receptor subtypes.

  4. Nucleobases and Prebiotic Molecules in Organic Residues Produced from the Ultraviolet Photo-Irradiation of Pyrimidine in NH3 and H2O+NH3 Ices

    Science.gov (United States)

    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.

  5. Stereoselective synthesis of 2'-purine and pyrimidine derivatives of 1',4'-anhydro-2'-deoxy D-arabitol and D-altritol

    Institute of Scientific and Technical Information of China (English)

    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.

  6. Synthesis of New Bis-Alkylated Phosphono Alkenyl Acyclonucleosides : (Z and (E-Diethyl-2-(3-alkyl pyrimidin-1-ylethylen-1-yl Phosphonate

    Directory of Open Access Journals (Sweden)

    J. L. Imbach

    2000-10-01

    Full Text Available The E- and Z- phosphonoalkenyl acyclonucleosides of uracil and thymine were synthesized under Michael addition conditions. Introduction of an alkyl, alkenyl or alkynyl group at the N-3 position of the pyrimidine moiety was accomplished using potassium carbonate in DMF.

  7. One-pot synthesis of novel 1H-pyrimido[4,5-c][1,2]diazepines and pyrazolo[3,4-d]pyrimidines

    Directory of Open Access Journals (Sweden)

    Gogoi Baikuntha J

    2006-03-01

    Full Text Available Abstract Novel 1H-pyrimido [4,5-c][1,2]diazepines 3 & 4 and pyrazolo [3,4-d]pyrimidines 6 were regioselectively synthesised by the reaction of 1,3-dimethyl-6-hydrazinouracils 1 with various α,β-unsaturated compounds 2 and α-ketoalkynes 8 in excellent yields.

  8. One-pot synthesis of novel 1H-pyrimido[4,5-c][1,2]diazepines and pyrazolo[3,4-d]pyrimidines

    Science.gov (United States)

    Prajapati, Dipak; Baruah, Partha P; Gogoi, Baikuntha J; Sandhu, Jagir S

    2006-01-01

    Novel 1H-pyrimido [4,5-c][1,2]diazepines 3 & 4 and pyrazolo [3,4-d]pyrimidines 6 were regioselectively synthesised by the reaction of 1,3-dimethyl-6-hydrazinouracils 1 with various α,β-unsaturated compounds 2 and α-ketoalkynes 8 in excellent yields. PMID:16556308

  9. A Novel and Efficient Five-Component Synthesis of Pyrazole Based Pyrido[2,3-d]pyrimidine-diones in Water: A Triply Green Synthesis

    Directory of Open Access Journals (Sweden)

    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.

  10. New Ideas on Labeling Schemes

    DEFF Research Database (Denmark)

    Rotbart, Noy Galil

    evaluation of fully dynamic labeling schemes. Due to a connection between adjacency labeling schemes and the graph theoretical study of induced universal graphs, we study these in depth and show novel results for bounded degree graphs and power-law graphs. We also survey and make progress on the related......With ever increasing size of graphs, many distributed graph systems emerged to store, preprocess and analyze them. While such systems ease up congestion on servers, they incur certain penalties compared to centralized data structure. First, the total storage required to store a graph...... in a distributed fashion increases. Second, attempting to answer queries on vertices of a graph stored in a distributed fashion can be significantly more complicated. In order to lay theoretical foundations to the first penalty mentioned a large body of work concentrated on labeling schemes. A labeling scheme...

  11. Off-Label Drug Use

    Science.gov (United States)

    ... it’s not legal for drug companies to market (advertise or promote) their drugs for off-label uses. ... Statistics Center Volunteer Learning Center Follow Us Twitter Facebook Instagram Cancer Information, Answers, and Hope. Available Every ...

  12. Sustainability labels on food products

    DEFF Research Database (Denmark)

    Grunert, Klaus G; Hieke, Sophie; Wills, Josephine

    2014-01-01

    of sustainability was limited, but understanding of four selected labels (Fair Trade, Rainforest Alliance, Carbon Footprint, and Animal Welfare) was better, as some of them seem to be self-explanatory. The results indicated a low level of use, no matter whether use was measured as self-reported use of different......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...

  13. Probing the metabolic network in bloodstream-form Trypanosoma brucei using untargeted metabolomics with stable isotope labelled glucose.

    Directory of Open Access Journals (Sweden)

    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.

  14. SYNTHESIS OF CHALCONES, 1, 3-THIAZINES AND 1, 3-PYRIMIDINES DERIVATIVES AND THEIR BIOLOGICAL EVALUATION FOR ANTIINFLAMMATORY, ANALGESIC AND ULCEROGENIC ACTIVITY SYNTHESIS von Chalkonen, 1, 3-Thiazine AND 1, 3-PYRIMIDINE DERIVATE UND IHRE BIOLOGISCHE EVALUATION FOR entzündungshemmende, schmerzstillende und ulcerogene ACTIVITY

    Directory of Open Access Journals (Sweden)

    Vijay V. Dabholkar and Sagar D. Parab

    2011-08-01

    Full Text Available Series of chalcones 2 and 2-amino-4-(2'-amino-5'-substitued phenylmercapto-6-phenyl pyrimidine 3, 2-substituted guanidino-4-(2'-amino-5'-substitued phenylmercapto-6-phenyl-1, 3- thiazine 4, Schiff base of 2-amino-4-(2'-amino-5'-substitued phenylmercapto-6-phenyl pyrimidine 5, 2-[2"-(substituted phenyl-4"-oxo-5"H-thiazol-3"-yl-4-{2'-[2"'- (substitutedphenyl-4"'-oxo-5"'H-thiazol-3"'-yl]-5'-substitued phenyl}mercapto-6-phenyl pyrimidine 6 were synthesized and studied by IR, NMR and Mass spectroscopy. The new products showed anti-inflammatory, analgesic, and ulcerogenic activities comparable to that of indomethacin and acetylsalicylic acid, respectively.

  15. How to Read a Nutrition Facts Label

    Medline Plus

    Full Text Available ... Smart About Social Media How to Read a Nutrition Facts Label (Video) KidsHealth > For Parents > How to Read a Nutrition Facts Label (Video) Print A A A en ... nutricionales (video) Most packaged foods come with a Nutrition Facts label. These labels have a lot of ...

  16. How to Read a Nutrition Facts Label

    Medline Plus

    Full Text Available ... Games, and the Internet How to Read a Nutrition Facts Label (Video) KidsHealth > For Parents > How to Read a Nutrition Facts Label (Video) Print A A A en ... nutricionales (video) Most packaged foods come with a Nutrition Facts label. These labels have a lot of ...

  17. DSm Vector Spaces of Refined Labels

    CERN Document Server

    Kandasamy, W B Vasantha

    2011-01-01

    In this book the authors introduce the notion of DSm vector spaces of refined labels. They also realize the refined labels as a plane and a n-dimensional space. Further, using these refined labels, several algebraic structures are defined. Finally DSm semivector space or refined labels is described. Authors also propose some research problems.

  18. How to Read a Nutrition Facts Label

    Medline Plus

    Full Text Available ... and the Internet How to Read a Nutrition Facts Label (Video) KidsHealth > For Parents > How to Read a Nutrition Facts Label (Video) Print A A A en español ... video) Most packaged foods come with a Nutrition Facts label. These labels have a lot of important ...

  19. How to Read a Nutrition Facts Label

    Medline Plus

    Full Text Available ... to 2-Year-Old How to Read a Nutrition Facts Label (Video) KidsHealth > For Parents > How to Read a Nutrition Facts Label (Video) Print A A A en ... nutricionales (video) Most packaged foods come with a Nutrition Facts label. These labels have a lot of ...

  20. 21 CFR 606.121 - Container label.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 7 2010-04-01 2010-04-01 false Container label. 606.121 Section 606.121 Food and... Container label. (a) The container label requirements are designed to facilitate the use of a uniform container label for blood and blood components (except Source Plasma) by all blood establishments. (b)...

  1. New AIE-active pyrimidine-based boronfluoride complexes with high solid-state emission and reversible mechanochromism luminescence behavior.

    Science.gov (United States)

    Qi, Fen; Lin, Jianjian; Wang, Xiaoqing; Cui, Peng; Yan, Hui; Gong, Shuwen; Ma, Chunlin; Liu, Zhipeng; Huang, Wei

    2016-04-25

    A new family of pyrimidine-based BF2 complexes () with aggregation-induced emission (AIE) and mechanochromic luminescence properties were developed. These compounds exhibit intense fluorescence in their aggregation/solid-state resulting from their large Stokes shift and AIE. X-ray crystallographic analysis shows that the weak intermolecular interactions by fixing the molecular conformations of are responsible for the intense fluorescence in solid-state. In addition to their pronounced AIE behaviour, also exhibits a reversible chromic response to grinding, and a distinct red-shift of emission is observed. The high solid-state luminescence and grinding-stimuli response properties of these compounds make them potential candidates for smart materials.

  2. Design and Synthesis of a Series of Pyrido[2,3-d]pyrimidine Derivatives as CCR4 Antagonists

    Directory of Open Access Journals (Sweden)

    Ying Wang

    2012-08-01

    Full Text Available A series of pyrido[2,3-d]pyrimidine derivatives were designed and synthesized based on known CC chemokine receptor 4 (CCR4 antagonists. The activities of all the newly synthesized compounds were evaluated using a chemotaxis inhibition assay. Compound 6b was proven to be a potent CCR4 antagonist that can block cell chemotaxis induced by macrophage-derived chemokine (MDC, thymus and activation regulated chemokine (TARC, and CKLF1, the natural ligands of CCR4. In addition, compound 6b is more effective than budesonide in the murine rhinitis model. The intravenous injection LD50 of compound 6b is 175 mg/kg and the oral LD50 is greater than 2,000 mg/kg.

  3. Nuclear dynamics investigation of the initial electron transfer in the cyclobutane pyrimidine dimer lesion repair process by photolyases

    CERN Document Server

    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...

  4. Duplex and triplex formation of mixed pyrimidine oligonucleotides with stacking of phenyl-triazole moieties in the major groove

    DEFF Research Database (Denmark)

    Andersen, Nicolai Krog; Døssing, Holger Balslev; Jensen, Frank;

    2011-01-01

    5-(1-Phenyl-1,2,3-triazol-4-yl)-2'-deoxycytidine was synthesized from a modified CuAAC protocol and incorporated into mixed pyrimidine oligonucleotide sequences together with the corresponding 5-(1-phenyl-1,2,3-triazol-4-yl)-2'-deoxyuridine. With consecutive incorporations of the two modified...... nucleosides, improved duplex formation with a complementary RNA and improved triplex formation with a complementary DNA duplex were observed. The improvement is due to π-π stacking of the phenyl-triazole moieties in the major groove. The strongest stacking and most pronounced positive influence on thermal...... stability was found in between the uridine analogues or with the cytidine analogue placed in the 3' direction to the uridine analogue. Modeling indicated a different orientation of the phenyl-triazole moieties in the major groove to account for the difference between the two nucleotides. The modified...

  5. Experimental and theoretical investigation of the triple differential cross section for electron impact ionization of pyrimidine molecules.

    Science.gov (United States)

    Builth-Williams, J D; Bellm, S M; Jones, D B; Chaluvadi, Hari; Madison, D H; Ning, C G; Lohmann, B; Brunger, M J

    2012-01-14

    Cross-section data for electron impact induced ionization of bio-molecules are important for modelling the deposition of energy within a biological medium and for gaining knowledge of electron driven processes at the molecular level. Triply differential cross sections have been measured for the electron impact ionization of the outer valence 7b(2) and 10a(1) orbitals of pyrimidine, using the (e, 2e) technique. The measurements have been performed with coplanar asymmetric kinematics, at an incident electron energy of 250 eV and ejected electron energy of 20 eV, for scattered electron angles of -5°, -10°, and -15°. The ejected electron angular range encompasses both the binary and recoil peaks in the triple differential cross section. Corresponding theoretical calculations have been performed using the molecular 3-body distorted wave model and are in reasonably good agreement with the present experiment.

  6. Nitrogen K-edge x-ray absorption near edge structure of pyrimidine-containing nucleotides in aqueous solution.

    Science.gov (United States)

    Shimada, Hiroyuki; Minami, Hirotake; Okuizumi, Naoto; Sakuma, Ichiro; Ukai, Masatoshi; Fujii, Kentaro; Yokoya, Akinari; Fukuda, Yoshihiro; Saitoh, Yuji

    2015-05-07

    X-ray absorption near edge structure (XANES) was measured at energies around the N K-edge of the pyrimidine-containing nucleotides, cytidine 5'-monophosphate (CMP), 2'-deoxythymidine 5'-monophosphate (dTMP), and uridine 5'-monophosphate (UMP), in aqueous solutions and in dried films under various pH conditions. The features of resonant excitations below the N K-edge in the XANES spectra for CMP, dTMP, and UMP changed depending on the pH of the solutions. The spectral change thus observed is systematically explained by the chemical shift of the core-levels of N atoms in the nucleobase moieties caused by structural changes due to protonation or deprotonation at different proton concentrations. This interpretation is supported by the results of theoretical calculations using density functional theory for the corresponding nucleobases in the neutral and protonated or deprotonated forms.

  7. Nitrogen K-edge x-ray absorption near edge structure of pyrimidine-containing nucleotides in aqueous solution

    Energy Technology Data Exchange (ETDEWEB)

    Shimada, Hiroyuki, E-mail: hshimada@cc.tuat.ac.jp; Minami, Hirotake; Okuizumi, Naoto; Sakuma, Ichiro; Ukai, Masatoshi [Department of Applied Physics, Tokyo University of Agriculture and Technology, Koganei-shi, Tokyo 184-8588 (Japan); Fujii, Kentaro; Yokoya, Akinari [Advanced Science Research Center, Japan Atomic Energy Agency, Tokai-mura, Naka-gun, Ibaraki 319-1195 (Japan); Fukuda, Yoshihiro; Saitoh, Yuji [Synchrotron Radiation Research Center, Japan Atomic Energy Agency, Sayo-gun, Hyogo 679-5148 (Japan)

    2015-05-07

    X-ray absorption near edge structure (XANES) was measured at energies around the N K-edge of the pyrimidine-containing nucleotides, cytidine 5′-monophosphate (CMP), 2′-deoxythymidine 5′-monophosphate (dTMP), and uridine 5′-monophosphate (UMP), in aqueous solutions and in dried films under various pH conditions. The features of resonant excitations below the N K-edge in the XANES spectra for CMP, dTMP, and UMP changed depending on the pH of the solutions. The spectral change thus observed is systematically explained by the chemical shift of the core-levels of N atoms in the nucleobase moieties caused by structural changes due to protonation or deprotonation at different proton concentrations. This interpretation is supported by the results of theoretical calculations using density functional theory for the corresponding nucleobases in the neutral and protonated or deprotonated forms.

  8. Synthesis and Crystal Structure of 4-(4,6-dimethoxyl -pyrimidin-2-yl)-3-thiourea Carboxylic Acid Methyl Ester

    Institute of Scientific and Technical Information of China (English)

    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.

  9. Bis[2-amino-6-methyl-pyrimidin-4(1H)-one-κN,O]dichloridocadmium(II).

    Science.gov (United States)

    Kaabi, Kamel; El Glaoui, Meher; Pereira Silva, P S; Ramos Silva, M; Ben Nasr, Cherif

    2010-09-08

    In the title compound, [CdCl(2)(C(5)H(7)N(3)O)(2)], the Cd(II) atom is six-coordinated by two heterocyclic N atoms [Cd-N = 2.261 (2) and 2.286 (2) Å] and two O atoms [Cd-O = 2.624 (2) and 2.692 (2) Å] from two bidentate chelate 2-amino-6-methyl-pyrimidin-4(1H)-one ligands and two chloride ions [Cd-Cl = 2.4674 (6) and 2.4893 (7) Å]. The crystal packing is characterized by an open-framework architecture with the crystal packing stabilized by inter-molecular N-H⋯Cl and N-H⋯O hydrogen bonds.

  10. Crystal structure of 1-ethylpyrazolo[3,4-d]pyrimidine-4(5H-thione

    Directory of Open Access Journals (Sweden)

    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.

  11. Kinetics and mechanism of electron-induced splitting of a cyclobutane pyrimidine dimer with or without an electron acceptor

    Institute of Scientific and Technical Information of China (English)

    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.

  12. A brief history of cell labelling

    Energy Technology Data Exchange (ETDEWEB)

    Peters, A.M. [Royal Sussex Country Hospital, Brighton (United Kingdom)

    2005-12-15

    The term cell labelling is usually used in the context of labelled leukocytes for imaging inflammation and labelled platelets for imaging thrombosis. Erythrocyte labelling for in vitro measurements of red cell life span, in vivo measurements of splenic red cell pooling, radionuclide ventriculography and imaging sites of bleeding has developed rather separately and has a different history. Labelled platelets and leukocytes were originally developed for cell kinetic studies. Since the current-day applications of labelled platelets and leukocytes depend on a clear understanding of cell kinetics, these classical studies are important and relevant to the history of cell labelling.

  13. An Optimal Labeling Scheme for Ancestry Queries

    OpenAIRE

    2009-01-01

    An ancestry labeling scheme assigns labels (bit strings) to the nodes of rooted trees such that ancestry queries between any two nodes in a tree can be answered merely by looking at their corresponding labels. The quality of an ancestry labeling scheme is measured by its label size, that is the maximal number of bits in a label of a tree node. In addition to its theoretical appeal, the design of efficient ancestry labeling schemes is motivated by applications in web search engines. For this p...

  14. Photoaffinity Labeling of Plasma Proteins

    Directory of Open Access Journals (Sweden)

    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.

  15. Molecular interaction of the first 3 enzymes of the de novo pyrimidine biosynthetic pathway of Trypanosoma cruzi

    Energy Technology Data Exchange (ETDEWEB)

    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.

  16. Stretches of alternating pyrimidine/purines and purines are respectively linked with pathogenicity and growth temperature in prokaryotes

    Directory of Open Access Journals (Sweden)

    Hardy Simon P

    2009-07-01

    Full Text Available Abstract Background The genomic fractions of purine (RR and alternating pyrimidine/purine (YR stretches of 10 base pairs or more, have been linked to genomic AT content, the formation of different DNA helices, strand-biased gene distribution, DNA structure, and more. Although some of these factors are a 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 phyla. RR stretches are overrepresented in all phyla except for the Actinobacteria and β-Proteobacteria. In contrast, YR tracts are underrepresented in all phyla except for the β-Proteobacterial group. YR-stretches are associated with phylum, pathogenicity and habitat, whilst RR-tracts are associated with phylum, AT content, oxygen requirement, growth temperature and halotolerance. All associations described were statistically significant with p . Conclusion Analysis of chromosomal distributions of RR/YR sequences in prokaryotes reveals a set of associations with environmental factors not observed with mono- and oligonucleotide frequencies. This implies that important information can be found in the distribution of RR/YR stretches that is more difficult to obtain from genomic mono- and oligonucleotide frequencies. The association between pathogenicity and fractions of YR stretches is assumed to be linked to recombination and horizontal transfer.

  17. The role of the de novo pyrimidine biosynthetic pathway in Cryptococcus neoformans high temperature growth and virulence

    Science.gov (United States)

    de Gontijo, Fabiano Assis; Pascon, Renata C.; Fernandes, Larissa; Machado, Joel; Alspaugh, J. Andrew; Vallim, Marcelo A

    2015-01-01

    Fungal infections are often difficult to treat due to the inherent similarities between fungal and animal cells and the resulting host toxicity from many antifungal compounds. Cryptococcus neoformans is an opportunistic fungal pathogen of humans that causes life-threatening disease, primarily in immunocompromised patients. Since antifungal therapy for this microorganism is limited, many investigators have explored novel drug targets aim at virulence factors, such as the ability to grow at mammalian physiological temperature (37°C). To address this issue, we used the Agrobacterium tumefaciens gene delivery system to create a random insertion mutagenesis library that was screened for altered growth at elevated temperatures. Among several mutants unable to grow at 37°C, we explored one bearing an interruption in the URA4 gene. This gene encodes dihydroorotase (DHOase) that is involved in the de novo synthesis of pyrimidine ribonucleotides. Loss of the C. neoformans Ura4 protein, by targeted gene interruption, resulted in an expected uracil/uridine auxotrophy and an unexpected high temperature growth defect. In addition, the ura4 mutant displayed phenotypic defects in other prominent virulence factors (melanin, capsule and phospholipase) and reduced stress response compared to wild type and reconstituted strains. Accordingly, this mutant had a decreased survival rate in macrophages and attenuated virulence in a murine model of cryptococcal infection. Quantitative PCR analysis suggests that this biosynthetic pathway is induced during the transition from 30°C to 37°C, and that transcriptional regulation of de novo and salvage pyrimidine pathway are under the control of the Ura4 protein. PMID:25011011

  18. CPU-12, a novel synthesized oxazolo[5,4-d]pyrimidine derivative, showed superior anti-angiogenic activity.

    Science.gov (United States)

    Liu, Jiping; Deng, Ya-Hui; Yang, Ling; Chen, Yijuan; Lawali, Manzo; Sun, Li-Ping; Liu, Yu

    2015-09-01

    Angiogenesis is a crucial requirement for malignant tumor growth, progression and metastasis. Tumor-derived factors stimulate formation of new blood vessels which actively support tumor growth and spread. Various of drugs have been applied to inhibit tumor angiogenesis. CPU-12, 4-chloro-N-(4-((2-(4-methoxyphenyl)-5-methyloxazolo[5,4-d] pyrimidin-7-yl)amino)phenyl)benzamide, is a novel oxazolo[5,4-d]pyrimidine derivative that showed potent activity in inhibiting VEGF-induced angiogenesis in vitro and ex-vivo. In cell toxicity experiments, CPU-12 significantly inhibited the human umbilical vein endothelial cell (HUVEC) proliferation in a dose-dependent manner with a low IC50 value at 9.30 ± 1.24 μM. In vitro, CPU-12 remarkably inhibited HUVEC's migration, chemotactic invasion and capillary-like tube formation in a dose-dependent manner. In ex-vivo, CPU-12 effectively inhibited new microvessels sprouting from the rat aortic ring. In addition, the downstream signalings of vascular endothelial growth factor receptor-2 (VEGFR-2), including the phosphorylation of PI3K, ERK1/2 and p38 MAPK, were effectively down-regulated by CPU-12. These evidences suggested that angiogenic response via the induction of VEGFR through distinct signal transduction pathways regulating proliferation, migration and tube formation of endothelial cells was significantly inhibited by the novel small molecule compound CPU-12 in vitro and ex-vivo. In conclusion, CPU-12 showed superior anti-angiogenic activity in vitro. Copyright © 2015 The Authors. Production and hosting by Elsevier B.V. All rights reserved.

  19. Modulating structural dimensionality of cadmium(II) coordination polymers by means of pyrazole, tetrazole and pyrimidine derivative ligands

    Science.gov (United States)

    Seco, Jose Manuel; Calahorro, Antonio; Cepeda, Javier; Rodríguez-Diéguez, Antonio

    2015-06-01

    Six new compounds with functionalized pyrazole, tetrazole, and pyrimidine ligands, namely [Cd(μ-4-Hampz)(μ-Cl)2]n(1), [Cd(μ3-pzdc)(μ-H2O)(H2O)]n(2), [Cd(μ-5-amtz)2(eda)]n(3), {[Cd9(μ4-5-amtz)8(μ-Cl)10(H2O)2]ṡxH2O}n(4), {[Cd2(μ-dm2-pmc)2Cl2(H2O)2]ṡH2O}n(5), and [Cd2(μ-Br2-pmc)(μ-Cl)3(H2O)2]n(6) (where 4-Hampz = 4-aminopyrazole, pzdc = 3,5-pyrazoledicarboxylate, 5-amtz = 5-aminotetrazolate, eda = ethylenediamine, dm2-pmc = 4,6-dimethoxy-2-pyrimidinecarboxylate, Br2-pmc = 5-bromopyrimidine-2-carboxylate) have been synthesized under hydrothermal conditions and structurally characterized by single crystal X-ray diffraction. Compounds 1 and 2 share the structural feature of being constructed from dinuclear building units that are further connected through the pyrazole based ligands, rendering a compact and a potentially open 3D frameworks, respectively. On the other hand, 5-amtz ligand exhibits two different coordination modes in compounds 3 and 4 as a result of the presence or absence of an additional blocking ligand. In this way, the μ-κ4N,N‧,N″,N‴ mode in 4 affords robust clusters that are joined in a topologically novel 3D open architecture containing two types of channels, whereas a simple bidentate bridging mode is limited for 5-amtz in 3 due to the presence of the chelating eda ligand. 1D and 3D structures are obtained with pyrimidine ligands in compounds 5 and 6 according to the steric hindrance of the substituents.

  20. 49 CFR 172.430 - POISON label.

    Science.gov (United States)

    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...

  1. Fibrinogen labelling with I-131

    Energy Technology Data Exchange (ETDEWEB)

    Seminario, C.; Capillo, T.; Montanez, J. (Instituto Peruano de Energia Nuclear, Lima)

    1983-05-01

    Of the different techniques of labelling liophylized human fibrinogen, the technique of mono-chloride with modified iodine was selected. The labelling of the molecule was performed in alkali media of buffalo glycine in which the solution of stable iodine will react as well as on a later stage will the radioactive isotope. The labelling processes which were undertaken with different activities had an efficiency of over 40%; when purification with resins amberlite was carried through, in none of the cases were the impurities over 5%. Daily controls till the seventh day showed that the average values of radiochemical purity decrease were lower than 1%. The specific activity as well as the concentration of I/sup 131/, the fibrinogen and other characteristics come up to the norms of the pharmacopoeia which are applied.

  2. Learning With Auxiliary Less-Noisy Labels.

    Science.gov (United States)

    Duan, Yunyan; Wu, Ou

    2016-04-06

    Obtaining a sufficient number of accurate labels to form a training set for learning a classifier can be difficult due to the limited access to reliable label resources. Instead, in real-world applications, less-accurate labels, such as labels from nonexpert labelers, are often used. However, learning with less-accurate labels can lead to serious performance deterioration because of the high noise rate. Although several learning methods (e.g., noise-tolerant classifiers) have been advanced to increase classification performance in the presence of label noise, only a few of them take the noise rate into account and utilize both noisy but easily accessible labels and less-noisy labels, a small amount of which can be obtained with an acceptable added time cost and expense. In this brief, we propose a learning method, in which not only noisy labels but also auxiliary less-noisy labels, which are available in a small portion of the training data, are taken into account. Based on a flipping probability noise model and a logistic regression classifier, this method estimates the noise rate parameters, infers ground-truth labels, and learns the classifier simultaneously in a maximum likelihood manner. The proposed method yields three learning algorithms, which correspond to three prior knowledge states regarding the less-noisy labels. The experiments show that the proposed method is tolerant to label noise, and outperforms classifiers that do not explicitly consider the auxiliary less-noisy labels.

  3. 78 FR 66826 - Prior Label Approval System: Generic Label Approval

    Science.gov (United States)

    2013-11-07

    ... product as ``organic'' or containing organic ingredients; (3) claims that are undefined in FSIS... labeling errors resulted from production mistakes, such as packaging the product in the wrong box. More... poultry products inspection regulations to expand the circumstances in which FSIS will generically...

  4. Denture labeling: A new approach

    Directory of Open Access Journals (Sweden)

    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.

  5. 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

    DEFF Research Database (Denmark)

    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)-one...

  6. Synthesis of 5,7-Dimethyl-2-(5-Substituted-l,3,4-Oxadiazole-2-yl)-Methylenethio-1,2,4-Triazolo[1,5-a]Pyrimidines as Potential Fungicides

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    A series of diheterocyclic compounds containing 1,2,4-triazolo [l,5-a]pyrimidine and 1,3,4-oxadiazole were designed and synthesized starting from 2-mercapto-5,7-dimethyl-l,2,4-triazolo [ 1,5-a] pyrimidine. The structure of all compounds prepared were confirmed by H NMR spectroscopy and elemental analysis. The preliminary bioassay indicated that the title compounds displayed good fungicidal activity against Rhizoctonia solani.

  7. Connected Component Labeling Using Components Neighbors-Scan Labeling Approach

    Directory of Open Access Journals (Sweden)

    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.

  8. Food quality labels from the producers’ perspective

    Directory of Open Access Journals (Sweden)

    Šárka Velčovská

    2016-09-01

    Full Text Available The paper deals with analysing the food producer attitudes towards quality labels. The Klasa label, as the most known and the most frequently used food quality label in the Czech Republic, have become the subject of investigation. The aim of the research was to identify the benefits and problems arising from the certification process and the label use. Primary data were collected in online survey based on standardized questionnaire. In census, 86 respondents from the total 218 producers with the Klasa label in the Czech Republic completed the questionnaire. The most of producers (72% have a longer experience with the label, they are using the label for more than four years. The producers’ expectations from the label were fulfilled only partially. A poor state marketing support and missing marketing strategy were identified as general problems of the label. Specific perceived problems are formalities connected with the certification process and certification of poor-quality products. Correlation analysis, t-test and Pearson chi-square test were calculated to discover relations between variables. The results of the study can be beneficial to both, food producers as well as administrator of the label. Identified problems could help them to improve marketing strategy of the label in order to manage the label in effective way and use all benefits arising from the certification. Administrator of the label should make the certification process more effective and transparent, promotion should be focused on the explanation to consumers what the Klasa label guarantees.

  9. Design, Synthesis, and Cytotoxicity of 5-Fluoro-2-methyl-6-(4-aryl-piperazin-1-yl Benzoxazoles

    Directory of Open Access Journals (Sweden)

    Thuraya Al-Harthy

    2016-09-01

    Full Text Available To design new compounds suitable as starting points for anticancer drug development, we have synthesized a novel series of benzoxazoles with pharmaceutically advantageous piperazine and fluorine moieties attached to them. The newly synthesized benzoxazoles and their corresponding precursors were evaluated for cytotoxicity on human A-549 lung carcinoma cells and non-cancer HepaRG hepatocyes. Some of these new benzoxazoles show potential anticancer activity, while two of the intermediates show lung cancer selective properties at low concentrations where healthy cells are unaffected, indicating a selectivity window for anticancer compounds.

  10. Crystallization and X-ray diffraction of 5'-fluoro-5'-deoxyadenosine synthase, a fluorination enzyme from Streptomyces cattleya.

    Science.gov (United States)

    Dong, Changjiang; Deng, Hai; Dorward, Mark; Schaffrath, Christoph; O'Hagan, David; Naismith, James H

    2003-12-01

    Organofluorine compounds are widely prepared throughout the chemicals industry, but their prepararion generally requires harsh fluorinating reagents and non-aqueous solvents. On the other hand, biology has hardly exploited organofluorine compounds. A very few organisms synthesize organofluorine metabolites, suggesting they have evolved a mechanism to overcome the kinetic desolvation barrier to utilizing F(-)(aq). Here, the purification and crystallization of an enzyme from Streptomyces cattleya which is responsible for the synthesis of the C-F bond during fluoroacetate and 4-fluorothreonine biosynthesis is reported. The protein crystallizes in space group C222(1), with unit-cell parameters a = 75.9, b = 130.3, c = 183.4 A, alpha = beta = gamma = 90 degrees. Data were recorded to 1.9 A at the ESRF. The structure of the protein should provide important insights into the biochemical process of C-F bond formation.

  11. 5-Fluoro-1-(prop-2-en-1-yl-2,3-dihydro-1H-indole-2,3-dione

    Directory of Open Access Journals (Sweden)

    Fatim-Zahrae Qachchachi

    2017-01-01

    Full Text Available The asymmetric unit of the title compound, C11H8FNO2, consists of two independent molecules having different conformations and associated through pairwise C—H...F hydrogen bonds. These units form `stairstep' stacks along the b-axis direction via π–π stacking interactions between dihydroindole moieties, with interplanar spacings of 3.578 (3 and 3.627 (3 Å. The stacks are tied together by weak C—H...O hydrogen bonds.

  12. Improving the energy labelling scheme

    DEFF Research Database (Denmark)

    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 strengthen...

  13. The Labelling Approach to Deviance.

    Science.gov (United States)

    Rains, Prudence M.; Kitsuse, John L.; Duster, Troy; Freidson, Eliot

    2003-01-01

    This reprint of one chapter from the 1975 text, "Issues in the Classification of Children" by Nicholas Hobbs and others, addresses the theoretical, methodological, and empirical issues involved in the "labeling" approach to the sociology of deviance. It examines the social process of classification, the use of classification in social agencies,…

  14. When Diagnostic Labels Mask Trauma

    Science.gov (United States)

    Foltz, Robert; Dang, Sidney; Daniels, Brian; Doyle, Hillary; McFee, Scott; Quisenberry, Carolyn

    2013-01-01

    A growing body of research shows that many seriously troubled children and adolescents are reacting to adverse life experiences. Yet traditional diagnostic labels are based on checklists of surface symptoms. Distracted by disruptive behavior, the common response is to medicate, punish, or exclude rather than respond to needs of youth who have…

  15. Psychological effectiveness of carbon labelling

    Science.gov (United States)

    Beattie, Geoffrey

    2012-04-01

    Despite the decision by supermarket-giant Tesco to delay its plan to add carbon-footprint information onto all of its 70,000 products, carbon labelling, if carefully designed, could yet change consumer behaviour. However, it requires a new type of thinking about consumers and much additional work.

  16. Labelling schemes: From a consumer perspective

    DEFF Research Database (Denmark)

    Juhl, Hans Jørn; Stacey, Julia

    2000-01-01

    . A recent MAPP study has investigated the value consumers attach the Government-controlled labels 'Ø-mærket' and 'Den Blå Lup' and the private supermarket label 'Mesterhakket' when they purchase minced meat. The results reveal four consumer segments that use labelling schemes for food products very....... The remaining consumers, about 55%, trust the institutions guaranteeing the labels and they use the labels as a signal without actually knowing the content of each label. Segment composition will probably change depending on the food group studied. It is therefore recommended that the different consumer types...

  17. Synthesis, Antibacterial and Antitubercular Activities of Some 5H-Thiazolo[3,2-a]pyrimidin-5-ones and Sulfonic Acid Derivatives

    Directory of Open Access Journals (Sweden)

    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.

  18. Synthesis and evaluation of new anti-microbial additive based on pyrimidine derivative incorporated physically into polyurethane varnish for surface coating and into printing ink paste

    Directory of Open Access Journals (Sweden)

    H. Abd El-Wahab

    2015-09-01

    Full Text Available In this study, heterocyclic compounds containing 3-((4-bromophenyldiazenyl-5-(methylthio-6-(phenylsulfonylpyrazolo-[1,5-a]pyrimidine-2,7-diamine (compound II and 4-(methylthio-3-phenylsulfonylbenzo[4,5]imidazo[1,2-a]pyrimidin-2-amine (compound III were prepared and their chemical structures were confirmed by spectral data. The new compounds were screened for antimicrobial activity against six different microbial strains when physically incorporated into polyurethane varnish formula and printing ink paste. Experimental coatings were manufactured on laboratory scale and applied by brush onto glass and steel panels. Results of the biological activity indicated that polyurethane varnishes and printing ink paste containing compounds II and III exhibit a very good antimicrobial effect. The physical and mechanical resistances of the polyurethane varnish formulations were also studied to evaluate any drawbacks associated with this addition. The studies revealed that the physical incorporation of compounds II and III enhances slightly the physical and mechanical properties.

  19. Solid supported microwave induced synthesis of imidazole–pyrimidine hybrids: Antimicrobial evaluation and docking study as 14DM-CPY51 inhibitors

    Directory of Open Access Journals (Sweden)

    Naziyanaz B. Pathan

    2016-09-01

    Full Text Available As part of our exploration for new antifungal agents, substituted 4,5-diphenyl imidazolyl pyrimidine hybrids were synthesized. A series of substituted ethyl 1,2,3,6-tetrahydro-4-methyl-2-oxo/thioxo-6-phenyl-1-(4,5-diphenyl-1-H-imidazol-2-yl pyrimidine-5-carboxylates have been studied for their binding active sites of cytochrome P450 14α-sterol demethylase CPY51 enzyme. For comparison, the binding behavior of known 14DM selective (Fluconazole and non-selective (Clotrimazole, Miconazole, Griesofulvin drugs has also been studied. Synthesized compounds were screened for their in vitro antibacterial activity against Staphylococcus aureus, Salmonella typhi, Pseudomonas aurogenosa and Klebsiella pneumonae and also antifungal activity against the opportunistic pathogens Candida albicans.

  20. Spectral and in vitro antimicrobial properties of 2-oxo-4-phenyl-6-styryl-1,2,3,4-tetrahydro-pyrimidine-5-carboxylic acid transition metal complexes

    Science.gov (United States)

    Dhankar, Raksha P.; Rahatgaonkar, Anjali M.; Chorghade, Mukund S.; Tiwari, Ashutosh

    2-oxo-4-phenyl-6-styryl-1,2,3,4-tetrahydro-pyrimidine-5-carboxylic acid (ADP) was complexed with acetates of Mn(II), Ni(II), Cu(II) and Zn(II). The structures of the ligand and its metal complexes were characterized by microanalysis, IR, NMR, UV-vis spectroscopy, magnetic susceptibility and TGA-DTA analyses. Octahedral and square planar geometries were suggested for the complexes in which the central metal ion coordinated with sbnd O donors of ligand and acetate ions. Each ligand binds the metal using carboxylate oxygens. The ligand and complexes were evaluated for their antimicrobial activities against different species of pathogenic bacteria and fungi. The present novel pyrimidine containing complexes could constitute a new group of antibacterial and antifungal agents.

  1. Synthesis of some novel pyrazolo[3,4-d] pyrimidin-4(5H-one derivatives as potential antimicrobial agent

    Directory of Open Access Journals (Sweden)

    Dipen K Sureja

    2016-01-01

    Full Text Available Objectives: The aim of the present work was to synthesize a novel series of pyrazolo[3,4-d]pyrimidin-4(5H-one derivatives and evaluate their in vitro antimicrobial activity. Methods: Cyclization of an ortho-amino ester of 1-(2,4-dinitrophenylpyrazole with various aliphatic/aromatic nitriles under different reaction conditions such as conventional and microwave assisted synthesis, provided pyrazolo[3,4-d] pyrimidin-4(5H-one derivatives. All the synthesized compounds were evaluated in vitro for their antimicrobial activity against selected bacteria and fungi by agar well diffusion method. Results: All newly synthesized compounds were characterized using spectral and elemental analysis. Compounds 2e, 2f, and 2g showed significant antimicrobial activity as compared to standard drugs used. Conclusion: The newly synthesized compounds could be useful templates for the design and optimization of more active analogs as a possible antimicrobial agent.

  2. An unusual correlation between ppGpp pool size and rate of ribosome synthesis during partial pyrimidine starvation of Escherichia coli

    DEFF Research Database (Denmark)

    Vogel, Ulla; Pedersen, Steen; Jensen, Kaj Frank

    1991-01-01

    Escherichia coli was exposed to partial pyrimidine starvation by feeding a pyrBI strain orotate as the only pyrimidine source. Subsequently, differential rates of synthesis of rRNA and of a few ribosome-associated proteins as well as the pool sizes of nucleoside triphosphates and ppGpp were...... at slow growth rates. Upshifts in growth rate were made by adding uracil to a culture growingslowly on orotate. Downshifts could be provoked by adding aspartate plus glutamate to a culture growing at a high concentration of orotate. Following the upshift, both the rates of synthesis of the ribosomal...

  3. VUV photophysics and dissociative photoionization of pyrimidine, purine, imidazole and benzimidazole in the 7-18 eV photon energy range

    Energy Technology Data Exchange (ETDEWEB)

    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.

  4. Synthesis of 4-aryl-4,5-dihydro-1-indeno[1,2-]pyrimidines by Biginelli condensation and their antibacterial activities

    Indian Academy of Sciences (India)

    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.

  5. Heterocyclic o-Aminonitriles: Preparation of Pyrazolo[3,4-d]-pyrimidines with Modification of the Substituents at the 1- Position

    Directory of Open Access Journals (Sweden)

    Samar A. Abubshait

    2001-06-01

    Full Text Available Novel 1-[6-(p-tolyl pyridazin-3-yl]pyrazole-o-aminonitriles (3a-c were formed using 3-hydrazino-6-(p-tolylpyridazine (2 and ketene S,S-acetals (1a, S,Nacetals (1b or tetracyanoethylene (1c. The pyrazole-o-aminonitriles (3a-c were in turn used as precursors for the preparation of previously unreported 1-[6-(p-tolyl-pyridazin-3-yl]pyrazolo[3,4-d]pyrimidines (8, 9, 13-20 and 7-[6-( p-tolyl pyridazin-3-yl]2-arylpyrazolo[3,4-d]1,2,4-triazolo[5,1-f]pyrimidines (10-12 which are expected to possess considerable chemical and pharmacological activities.

  6. Synthesis and applications of selectively {sup 13}C-labeled RNA

    Energy Technology Data Exchange (ETDEWEB)

    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).

  7. Facile and efficient synthesis of 5, 7-disubstituted thiazolo [5,4-d] pyrimidine-4, 6 (5H, 7H)-diones

    Institute of Scientific and Technical Information of China (English)

    Liang Chen; Zhan Mei Li; Jie Zhou; Hong Rui Song; Bai Ling Xu

    2012-01-01

    A facile and efficient approach was developed to access 5,7-disubstitued thiazolo[5,4-d]pyrimidine-4,6(5H,7H)-diones through condensation of N-substituted 5-amino-4-carbethoxythiazole with structurally diverse isocyanates in the presence of sodium hydride.The easy availability of substrates and tolerance of structural diversity in this reaction make it attractive to he used for constnuction of libraries in drug discovery process.

  8. Synthesis, Dimeric Crystal Structure, and Biological Activities of N-(4-Methyl-6-oxo-1,6-dihydro-pyrimidin-2-yl)-N-(2-trifluoromethyl-phenyl)-guanidine

    Institute of Scientific and Technical Information of China (English)

    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.

  9. 2,4-Diaminothieno[2,3-d]pyrimidine lipophilic antifolates as inhibitors of Pneumocystis carinii and Toxoplasma gondii dihydrofolate reductase.

    Science.gov (United States)

    Rosowsky, A; Papoulis, A T; Queener, S F

    1997-10-24

    Ten previously unreported 2,4-diaminothieno[2,3-d]pyrimidine lipophilic dihydrofolate reductase inhibitors were synthesized as potential inhibitors of Pneumocystis carinii and Toxoplasma gondii dihydrofolate reductase. Pivaloylation of 2,4-diamino-5-methylthieno[2,3-d]pyrimidine followed by dibromination with N-bromosuccinimide in the presence of benzoyl peroxide gave 2,4-bis(pivaloylamino)-6-bromo-5-(bromomethyl)thieno[2,3-d]pyrimid ine, which after condensation with substituted anilines or N-methylanilines and deprotection with base yielded 2,4-diamino-6-bromo-5-[(substituted anilino)methyl]thieno[2,3-d]pyrimidines. Removal of the 6-bromo substituent was accomplished with sodium borohydride and palladium chloride. The reaction yields were generally good to excellent. The products were tested as inhibitors of dihydrofolate reductase (DHFR) from P. carinii, T. gondii, and rat liver. Although the IC50 could not be reached for the 6-unsubstituted compounds because of their extremely poor solubility, three of the five 6-bromo derivatives were soluble enough to allow the IC50 to be determined against all three enzymes. 2,4-Diamino-5-[3,5-dichloro-4-(1-pyrrolo)anilino]methyl]- 6-bromothieno[2,3-d]pyrimidine was the most active of the 6-bromo derivatives, with an IC50 of 7.5 microM against P. carinii DHFR, but showed no selectivity for either P. carinii or T. gondii DHFR relative to the enzyme from rat liver.

  10. Efficient synthesis of 5,6-dihydrothieno[3',2':4,5]-thieno[2,3-d]pyrimidin-4(3H)-ones via an iminophosphorane

    Institute of Scientific and Technical Information of China (English)

    Yu Lu Chen; Yi Bo Nie; Ming Wu Ding

    2009-01-01

    5,6-Dihydrothieno[3',2':4,5]thieno[2,3-d]pyrimidin-4(3H)-ones 6 were synthesized in yields of 71-87% by a consecutive method,which includes aza-Wittig reaction of iminophosphorane 3 with aromatic isocynate to give carbodiimide 4 and subsequent reaction of 4 with various amines,phenols or alcohols in the presence of catalytic amount of sodium ethoxide or solid potassium carbonate.

  11. A Solution-Phase Parallel Synthesis of 5-Substituted 3,6-Dihydro-7H-1,2,3-triazolo[4,5-d]pyrimidin-7-ones

    Institute of Scientific and Technical Information of China (English)

    Sun Shaofa; Chen Li; Yang Xuhong

    2011-01-01

    5-Substituted 7H-1,2,3-triazolo[4,5-d]pyrimidin-7-ones (4) were rapidly prepared by a solution-phase parallel synthetic method, which includes aza-Wittig reaction of iminophosphorane (1) with phenyl isocynate to give car-bodiimide (2) and subsequent reaction of 2 with various amine and alcohols in the presence of catalytic amount of sodium alkoxide in a parallel fashion.

  12. Pyridinium Trifluoro Acetate Mediated Synthesis of 3,4-Dihydropyrimidin-2(1H-ones and Tetrazolo[1,5-a]pyrimidine-6-carboxylates

    Directory of Open Access Journals (Sweden)

    Radhakrishnan Sridhar

    2012-01-01

    Full Text Available A simple and economic synthesis of 3,4-dihydropyrimidin-2(1H-ones using pyridinium triflate as catalyst under microwave condition was attempted with an easy work-up protocol. Further tetrazolo [1,5-a] pyrimidine-6-carboxylates were synthesized by three-component coupling reaction of β-ketoesters with a mixture of aromatic aldehyde and 5-aminotetrazole. The products were well characterized with IR, NMR (1H and 13C NMR and mass spectrometry.

  13. Novel Synthesis and Anti-HIV-1 Activity of 2-Arylthio-6-benzyl-2,3-dihydro-1H-pyrimidin-4-ones (Aryl S-DABOs)

    DEFF Research Database (Denmark)

    Aly, Youssef L.; Pedersen, Erik Bjerreg.; La Colla, Paolo;

    2007-01-01

    The synthesis and the anti-HIV-1 activity of a series of 2-arylthio-6-benzyl-2,3-dihydro-1H-pyrimidin-4-ones (aryl S-DABOs) are reported. These compounds were synthesized via a coupling reaction of the corresponding 6-benzyl-2-thiouracils with aryl iodides in the presence of neocuproine hydrate......, copper(I) iodide, and sodium tert-butoxide. Target compounds showed moderate activity against HIV-1....

  14. Structure-based optimization of pyrazolo[3,4-d]pyrimidines as Abl inhibitors and antiproliferative agents toward human leukemia cell lines.

    Science.gov (United States)

    Manetti, Fabrizio; Brullo, Chiara; Magnani, Matteo; Mosci, Francesca; Chelli, Beatrice; Crespan, Emmanuele; Schenone, Silvia; Naldini, Antonella; Bruno, Olga; Trincavelli, Maria Letizia; Maga, Giovanni; Carraro, Fabio; Martini, Claudia; Bondavalli, Francesco; Botta, Maurizio

    2008-03-13

    Results from molecular docking calculations and Grid mapping laid the foundations for a structure-based optimization approach to improve the biological properties of pyrazolo-pyrimidine derivatives in terms of inhibition of Abl enzymatic activity and antiproliferative properties toward human leukemia cells. Insertion of halogen substituents with various substitution patterns, suggested by simulations, led to a significant improvement of leukemia cell growth inhibition and to an increase up to 1 order of magnitude of the affinity toward Abl.

  15. New pyrazolo-[3,4-d]-pyrimidine derivative Src kinase inhibitors lead to cell cycle arrest and tumor growth reduction of human medulloblastoma cells

    Science.gov (United States)

    Rossi, Alessandra; Schenone, Silvia; Angelucci, Adriano; Cozzi, Martina; Caracciolo, Valentina; Pentimalli, Francesca; Puca, Andrew; Pucci, Biagio; La Montagna, Raffaele; Bologna, Mauro; Botta, Maurizio; Giordano, Antonio

    2010-01-01

    Medulloblastoma is the most common malignant brain tumor in children, and despite improvements in the overall survival rate, it still lacks an effective treatment. Src plays an important role in cancer, and recently high Src activity was documented in medulloblastoma. In this report, we examined the effects of novel pyrazolo-[3,4-d]-pyrimidine derivative Src inhibitors in medulloblastoma. By MTS assay, we showed that the pyrimidine derivatives indicated as S7, S29, and SI163 greatly reduce the growth rate of medulloblastoma cells by inhibiting Src phosphorylation, compared with HT22 non-neoplastic nerve cells. These compounds also halt cells in the G2/M phase, and this effect likely occurs through the regulation of cdc2 and CDC25C phosphorylation, as shown by Western blot. Moreover, the exposure to pyrimidine derivatives induces apoptosis, assayed by the supravital propidium iodide assay, through modulation of the apoptotic proteins Bax and Bcl2, and inhibits tumor growth in vivo in a mouse model. Notably, S7, S29, and SI163 show major inhibitory effects on medulloblastoma cell growth compared with the chemotherapeutic agents cisplatin and etoposide. In conclusion, our results suggest that S7, S29, and SI163 could be novel attractive candidates for the treatment of medulloblastoma or tumors characterized by high Src activity.—Rossi, A., Schenone, S., Angelucci, A., Cozzi, M., Caracciolo, V., Pentimalli, F., Puca, A., Pucci, B., La Montagna, R., Bologna, M., Botta, M., Giordano, A. New pyrazolo-[3,4-d]-pyrimidine derivative Src kinase inhibitors lead to cell cycle arrest and tumor growth reduction of human medulloblastoma cells. PMID:20354138

  16. Synthesis and In Vitro Antimicrobial, Anthelmintic and Insecticidal Activities Study of 4(4'-Bromophenyl-6-substituted-aryl-1-acetyl pyrimidine-2-thiols

    Directory of Open Access Journals (Sweden)

    Rita Bamnela

    2010-01-01

    Full Text Available A new series of 4(4'-bromophenyl-6-substituted aryl-1-acetyl pyrimidine-2-thiol derivatives were synthesized by heating chalcones with thiourea, in the presence of ethanolic potassium hydroxide, followed by treatment with acetyl chloride. The structure of the compounds was characterized by IR and H1 NMR spectral study and elemental analysis. The compounds were screened for their antimicrobial, anthelmintic and insecticidal activities. All the compounds exhibited significant to moderate biological activities.

  17. Catalyst free synthesis of fused pyrido[2,3-d]pyrimidines and pyrazolo[3,4-b]pyridines in water

    Institute of Scientific and Technical Information of China (English)

    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.

  18. Regioselective multi-component synthesis of 1H-pyrazolo[3,4-d]pyrimidine-6(7H)-thiones.

    Science.gov (United States)

    Safaei, Shirin; Mohammadpoor-Baltork, Iraj; Khosropour, Ahmad Reza; Moghadam, Majid; Tangestaninejad, Shahram; Mirkhani, Valiollah

    2012-08-01

    A variety of pyrazolo[3,4-d]pyrimidine-6(7H)-thione derivatives were easily synthesized with a novel, simple, efficient, and regioselective method via three-component condensation reaction of 5-methyl-1H-pyrazol-3-amine, arylisothiocyanates, and aldehydes in the presence of catalytic amount of p-toluenesulfonic acid (p-TSA) in 1-butyl-3-methylimidazolium bromide ionic liquid with excellent yields and short reaction times.

  19. Pyrazolo[4,3-d]pyrimidine bioisostere of roscovitine: evaluation of a novel selective inhibitor of cyclin-dependent kinases with antiproliferative activity.

    Science.gov (United States)

    Jorda, Radek; Havlícek, Libor; McNae, Iain W; Walkinshaw, Malcolm D; Voller, Jirí; Sturc, Antonín; Navrátilová, Jana; Kuzma, Marek; Mistrík, Martin; Bártek, Jirí; Strnad, Miroslav; Krystof, Vladimír

    2011-04-28

    Inhibition of cyclin-dependent kinases (CDKs) with small molecules has been suggested as a strategy for treatment of cancer, based on deregulation of CDKs commonly found in many types of human tumors. Here, a new potent CDK2 inhibitor with pyrazolo[4,3-d]pyrimidine scaffold has been synthesized, characterized, and evaluated in cellular and biochemical assays. 7-Benzylamino-5(R)-[2-(hydroxymethyl)propyl]amino-3-isopropyl-1(2)H-pyrazolo[4,3-d]pyrimidine, compound 7, was prepared as a bioisostere of the well-known CDK inhibitor roscovitine. An X-ray crystal structure of compound 7 bound to CDK2 has been determined, revealing a binding mode similar to that of roscovitine. Protein kinase selectivity profile of compound 7 and its biological effects (cell cycle arrest, dephosphorylation of the retinoblastoma protein, accumulation of the tumor suppressor protein p53, induction of apoptosis, inhibition of homologous recombination) are consistent with CDK inhibition as a primary mode of action. Importantly, as the anticancer activities of the pyrazolo[4,3-d]pyrimidine 7 exceed those of its bioisostere roscovitine, compound 7 reported here may be preferable for cancer therapy.

  20. The EGF repeat-specific O-GlcNAc-transferase Eogt interacts with notch signaling and pyrimidine metabolism pathways in Drosophila.

    Directory of Open Access Journals (Sweden)

    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.

  1. 2-Arylpyrazolo[4,3-d]pyrimidin-7-amino derivatives as new potent and selective human A3 adenosine receptor antagonists. Molecular modeling studies and pharmacological evaluation.

    Science.gov (United States)

    Squarcialupi, Lucia; Colotta, Vittoria; Catarzi, Daniela; Varano, Flavia; Filacchioni, Guido; Varani, Katia; Corciulo, Carmen; Vincenzi, Fabrizio; Borea, Pier Andrea; Ghelardini, Carla; Di Cesare Mannelli, Lorenzo; Ciancetta, Antonella; Moro, Stefano

    2013-03-28

    On the basis of our previously reported 2-arylpyrazolo[4,3-d]pyrimidin-7-ones, a set of 2-arylpyrazolo[4,3-d]pyrimidin-7-amines were designed as new human (h) A3 adenosine receptor (AR) antagonists. Lipophilic groups with different steric bulk were introduced at the 5-position of the bicyclic scaffold (R5 = Me, Ph, CH2Ph), and different acyl and carbamoyl moieties (R7) were appended on the 7-amino group, as well as a para-methoxy group inserted on the 2-phenyl ring. The presence of acyl groups turned out to be of paramount importance for an efficient and selective binding at the hA3 AR. In fact, most of the 7-acylamino derivatives showed low nanomolar affinity (Ki = 2.5-45 nM) and high selectivity toward this receptor. A few selected pyrazolo[4,3-d]pyrimidin-7-amides were effective in counteracting oxaliplatin-induced apoptosis in rat astrocyte cell cultures, an in vitro model of neurotoxicity. Through an in silico receptor-driven approach the obtained binding data were rationalized and the molecular bases of the observed hA3 AR affinity and hA3 versus hA2A AR selectivity were explained.

  2. Structural refinement of pyrazolo[4,3-d]pyrimidine derivatives to obtain highly potent and selective antagonists for the human A3 adenosine receptor.

    Science.gov (United States)

    Squarcialupi, Lucia; Catarzi, Daniela; Varano, Flavia; Betti, Marco; Falsini, Matteo; Vincenzi, Fabrizio; Ravani, Annalisa; Ciancetta, Antonella; Varani, Katia; Moro, Stefano; Colotta, Vittoria

    2016-01-27

    In previous research, we identified some 7-oxo- and 7-acylamino-substituted pyrazolo[4,3-d]pyrimidine derivatives as potent and selective human (h) A3 adenosine receptor (AR) antagonists. Herein we report on the structural refinement of this class of antagonists aimed at achieving improved receptor-ligand recognition. Hence, substituents with different steric bulk, flexibility and lipophilicity (Me, Ar, heteroaryl, CH2Ph) were introduced at the 5- and 2-positions of the bicyclic scaffold of both the 7-oxo and 7-amino derivatives, and acyl residues were appended on the 7-amino group of the latter. All the 2-phenylpyrazolo[4,3-d]pyrimidin-7-amines and 7-acylamines bearing a 4-methoxyphenyl- or a 2-thienyl group at the 5-position showed high hA3 affinity and selectivity. In particular, the 2-phenyl-5-(2-thienyl)-pyrazolo[4,3-d]pyrimidin-7-(4-methoxybenzoyl)amine 25 (Ki = 0.027 nM) is one of the most potent and selective hA3 antagonists reported so far. By using an in silico receptor-driven approach the obtained binding data were rationalized and the molecular bases of the observed hA3 AR affinities were critically described.

  3. Ivabradine: A Review of Labeled and Off-Label Uses.

    Science.gov (United States)

    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.

  4. How to Read a Nutrition Facts Label

    Medline Plus

    Full Text Available ... General Health Growth & Development Infections Diseases & Conditions Pregnancy & ... leer las etiquetas de datos nutricionales (video) Most packaged foods come with a Nutrition Facts label. These labels ...

  5. 99mTc: Labeling Chemistry and Labeled Compounds

    Science.gov (United States)

    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

  6. Study on New Process of Synthesizing Pyrimidine%嘧啶合成新工艺研究

    Institute of Scientific and Technical Information of China (English)

    魏常喜; 戴立言; 王晓钟; 陈英奇

    2009-01-01

    研究了重要的医药中间体嘧啶的合成工艺,以尿素和丙二酸二乙酯为原料,在甲醇钠催化下合成巴比妥酸,并用三氯氧磷在N,N-二甲基苯胺催化下加氯成2,4,6-三氯嘧啶,将2,4,6-三氯嘧啶以钯碳催化,加氢脱氯得到嘧啶.得出每一步的最佳工艺条件,巴比妥酸合成:配料摩尔比1:1.1:1.2(丙二酸二乙酯:尿素:甲醇钠),回流,2 h;2,4,6-三氯嘧啶合成:配料摩尔比5:1(三氯氧磷:巴比妥酸),100~105℃,2 h;嘧啶合成:配料摩尔比5:1(氧化镁:2,4,6-三氯嘧啶),溶剂体积比3:1(水:乙醇),0.1 MPa,14 h,60℃.%The new process of preparing pyrimidine which is widely used as pharmaceutical intermediate was studied. Beginning from the raw material-- urea and diethyl malonate, barbituric acid was prepared with sodium methoxide as catalyst, then 2,4,6-trichloropyrimidine was synthesized by reacting of barbituric acid with phosphorus oxychloride in the presence of N,N-dimethylaniline. The object compound was prepared from 2,4,6-trichloropyrimidine by catalytic hydrogenation with palladium-charcoal as catalyst. The optimum reaction conditions for every reaction step were studied. For preparing barbituric acid, the mole ratio of diethyl malonate, urea and sodium methoxide was 1 : 1.1 : 1.2, and the mixture was refluxed 2 hours; for preparing 2,4,6-trichloropyrimidine, the mole ratio of phosphorus oxychloride and barbituric acid was 5 : 1, and the reaction was run at 100 - 105 ℃ for 2 hours; for preparing pyrimidine, the mole ratio of magnesium oxide and 2,4,6-trichloropyrimidine was 5 :1, the volume ratio of water and ethanol was 3 : 1 and the reaction was run at 0. 1 Mpa and 60 ℃ for 14 hours.

  7. Automatic Labelling of Topics with Neural Embeddings

    OpenAIRE

    Bhatia, Shraey; Lau, Jey Han; Baldwin, Timothy

    2016-01-01

    Topics generated by topic models are typically represented as list of terms. To reduce the cognitive overhead of interpreting these topics for end-users, we propose labelling a topic with a succinct phrase that summarises its theme or idea. Using Wikipedia document titles as label candidates, we compute neural embeddings for documents and words to select the most relevant labels for topics. Compared to a state-of-the-art topic labelling system, our methodology is simpler, more efficient, and ...

  8. SOME ECONOMIC IMPLICATIONS OF PUBLIC LABELING

    OpenAIRE

    2003-01-01

    This article discusses economic issues related to public labeling. The main contributions in both the empirical and theoretical literatures are presented in order to motivate responses to the questions, when should a regulator promote public labeling, and what are the limits to and the possible market distortions from public labeling? Although the issues are complicated, there is already much economic guidance that can be given to inform the policy debate over food labeling.

  9. ANTIMAGIC LABELING OF GENERALIZED SAUSAGE GRAPHS

    Directory of Open Access Journals (Sweden)

    Oudone Phanalasy

    2014-10-01

    Full Text Available An antimagic labeling of a graph with q edges is a bijection from the set of edges to the set of positive integers {1,2,...,q} such that all vertex weights are pairwise distinct, where the vertex weight of a vertex is the sum of the labels of all the edges incident with that vertex. A graph is antimagic if it has an antimagic labeling. In this paper we construct antimagic labeling for the family of generalized sausage graphs.

  10. White Label Space GLXP Mission

    Science.gov (United States)

    Barton, A.

    2012-09-01

    This poster presents a lunar surface mission concept and corresponding financing approach developed by the White Label Space team, an official competitor in the Google Lunar X PRIZE. The White Label Space team's origins were in the European Space Agency's ESTEC facility in the Netherlands. Accordingly the team's technical headquarters are located just outside ESTEC in the Space Business Park. The team has active partners in Europe, Japan and Australia. The team's goal is to provide a unique publicity opportunity for global brands to land on the moon and win the prestigious Google Lunar X PRIZE. The poster presents the main steps to achieve this goal, the cost estimates for the mission, describes the benefits to the potential sponsors and supporters, and details the progress achieved to date.

  11. Labeling nuclear DNA using DAPI.

    Science.gov (United States)

    Chazotte, Brad

    2011-01-01

    A number of fluorescent stains are available that label DNA and allow easy visualization of the nucleus in interphase cells and chromosomes in mitotic cells, including Hoechst, 4',6-diamidino-2-phenylindole (DAPI), ethidium bromide, propidium iodide, and acridine orange. Although not as bright as the vital Hoechst stains for DNA, DAPI has greater photostability. It is believed that DAPI associates with the minor groove of double-stranded DNA, with a preference for the adenine-thymine clusters. Cells must be permeabilized and/or fixed for DAPI to enter the cell and to bind DNA. Fluorescence increases approximately 20-fold when DAPI is bound to double-stranded DNA. This protocol describes the use of DAPI to label nuclear DNA of cells grown in culture.

  12. Tissue Specific Labeling in Proteomics

    Directory of Open Access Journals (Sweden)

    Evelyn Ramberger

    2017-07-01

    Full Text Available Mass spectrometry-based proteomics is a powerful tool for identifying and quantifying proteins in biological samples. While it is routinely used for the characterization of simple cell line systems, the analysis of the cell specific proteome in multicellular organisms and tissues poses a significant challenge. Isolating a subset of cells from tissues requires mechanical and biochemical separation or sorting, a process which can alter cellular signaling, and thus, the composition of the proteome. Recently, several approaches for cell selective labeling of proteins, that include bioorthogonal amino acids, biotinylating enzymes, and genetic tools, have been developed. These tools facilitate the selective labeling of proteins, their interactome, or of specific cell types within a tissue or an organism, while avoiding the difficult and contamination-prone biochemical separation of cells from the tissue. In this review, we give an overview of existing techniques and their application in cell culture models and whole animals.

  13. GdCl(3) catalysed Grieco condensation: a facile approach for the synthesis of novel pyrimidine and annulated pyrimidine fused indazole derivatives in single pot under mild conditions and their anti-microbial activity.

    Science.gov (United States)

    Yakaiah, T; Lingaiah, B P V; Narsaiah, B; Kumar, K Pranay; Murthy, U S N

    2008-02-01

    Indazole regioisomers such as 3-amino-4-(trifluoromethyl)-6-phenyl-1H-indazole-7-carbonitrile 1 and 3-amino-6-(trifluoromethyl)-4-phenyl-1H-indazole-7-carbonitrile 2 were independently reacted with formaldehyde followed by unsymmetrical, symmetrical and cyclic electron rich olefins in presence of GdCl(3) as catalyst and obtained pyrimidine fused indazole derivatives 3 and 4, respectively. The reaction is found to be concerted and an exclusive product is formed. Representative examples of compounds 3 and 4 were screened against Gram-positive, Gram-negative bacteria and fungal species such as yeast and filamentous fungi in vitro. Compound 3f showed significant activity against all species of Gram-positive and Gram-negative bacteria, whereas compounds 3h and 4a showed the least activity with reference to penicillin as well as streptomycin. Similarly compound 3c showed promising activity against yeast and filamentous fungi whereas compound 3f is inactive at the maximum concentration of 150 microg/mL.

  14. 2-Amino-4-methyl-6-oxo-3,6-dihydro-pyrimidin-1-ium perchlorate-2-amino-6-methyl-pyrimidin-4(1H)-one-water (1/1/1).

    Science.gov (United States)

    Kaabi, Kamel; El Glaoui, Maher; Ferretti, Valeria; Zeller, Matthias; Ben Nasr, Cherif

    2011-09-01

    In the title compound, C(5)H(8)N(3)O(+)·ClO(4) (-)·C(5)H(7)N(3)O·H(2)O, each perchlorate anion is paired with a protonated cationic 2-amino-6-methyl-pyrimidin-4(1H)-one and another non-protonated entity of the same organic pyrimidinone. The crystal structure is stabilized by N-H⋯O(org), N-H⋯O(water), N-H⋯O(ClO4), O-H⋯O(ClO4), N-H⋯N and C-H⋯O(ClO4) hydrogen bonds between the anions, organic entities and water mol-ecules. Inter-molecular π-π stacking inter-actions between neighbouring organic rings are observed with a face-to-face distance of 3.776 (2) Å, and O-H⋯O hydrogen bonds link the perchlorate anions and the water mol-ecules into chains along the b-axis direction. The perchlorate anion and the inter-stitial water mol-ecule are disordered over two mutually incompatible positions with a common occupancy ratio of 0.678 (16):0.322 (16).

  15. 2-Amino-4-methyl-6-oxo-3,6-dihydro­pyrimidin-1-ium perchlorate–2-amino-6-methyl­pyrimidin-4(1H)-one–water (1/1/1)

    Science.gov (United States)

    Kaabi, Kamel; El Glaoui, Maher; Ferretti, Valeria; Zeller, Matthias; Ben Nasr, Cherif

    2011-01-01

    In the title compound, C5H8N3O+·ClO4 −·C5H7N3O·H2O, each perchlorate anion is paired with a protonated cationic 2-amino-6-methyl­pyrimidin-4(1H)-one and another non-protonated entity of the same organic pyrimidinone. The crystal structure is stabilized by N—H⋯Oorg, N—H⋯Owater, N—H⋯OClO4, O—H⋯OClO4, N—H⋯N and C—H⋯OClO4 hydrogen bonds between the anions, organic entities and water mol­ecules. Inter­molecular π–π stacking inter­actions between neighbouring organic rings are observed with a face-to-face distance of 3.776 (2) Å, and O—H⋯O hydrogen bonds link the perchlorate anions and the water mol­ecules into chains along the b-axis direction. The perchlorate anion and the inter­stitial water mol­ecule are disordered over two mutually incompatible positions with a common occupancy ratio of 0.678 (16):0.322 (16). PMID:22065517

  16. POS Tagging Using Relaxation Labelling

    CERN Document Server

    Padro, L

    1995-01-01

    Relaxation labelling is an optimization technique used in many fields to solve constraint satisfaction problems. The algorithm finds a combination of values for a set of variables such that satisfies -to the maximum possible degree- a set of given constraints. This paper describes some experiments performed applying it to POS tagging, and the results obtained. It also ponders the possibility of applying it to word sense disambiguation.

  17. 16 CFR 1209.9 - Labeling requirement.

    Science.gov (United States)

    2010-01-01

    ... SAFETY STANDARD FOR CELLULOSE INSULATION The Standard § 1209.9 Labeling requirement. (a) Manufacturers, importers, and private labelers of cellulose insulation shall place on all containers of cellulose... corrosiveness of cellulose insulation. To meet this requirement manufacturers, importers, and private labelers...

  18. Politique de label et commerce international

    OpenAIRE

    2001-01-01

    This article investigates the effects of a public labelling system in a context of international trade. A simple framework allows to present some distortions linked to such a policy. A trade liberalisation situation may lead to a change in the label policy, where the foreign seller incurs the label cost. Classification JEL : F1, D8

  19. What determines consumer attention to nutrition labels?

    NARCIS (Netherlands)

    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

  20. DYNAMIC LABELING BASED FPGA DELAY OPTIMIZATION ALGORITHM

    Institute of Scientific and Technical Information of China (English)

    吕宗伟; 林争辉; 张镭

    2001-01-01

    DAG-MAP is an FPGA technology mapping algorithm for delay optimization and the labeling phase is the algorithm's kernel. This paper studied the labeling phase and presented an improved labeling method. It is shown through the experimental results on MCNC benchmarks that the improved method is more effective than the original method while the computation time is almost the same.

  1. Fluorescent Labeling of Nanometer Hydroxyapatite

    Institute of Scientific and Technical Information of China (English)

    Yuan ZHANG; Yuan YUAN; Changsheng LIU

    2008-01-01

    A novel surface treatment method using 3-aminopropyltriethoxysilane (AMPTES), was developed to immobilize the fluorescein molecule on nano-HAP (nanometer hydroxyapatite) powders. By pretreating the nano-HAP powders surface with AMPTES, fluorescein, chosen on the basis of the chemical structure of the nano- HAP powders, could be bound to the nano-HAP powders surface. The chemical compositions of nano-HAP before and after being labeled were characterized by Fourier transform infrared spectroscopy (FTIR) and X-ray photoelectron spectroscopy (XPS). The morphology, phase composition, and the fluorescence characteristics of the nano-HAP powders with and without staining were also investigated. The FTIR and XPS results revealed that fiuorescein had been successfully immobilized on the surface of AMPTES-bound nano-HAP powders via the acylamide bond formation between the -COOH of fluorescein and the -NH2 of AMPTES. The labeled nano-HAP powders possessed strong fluorescent intensity with a little deviation from the maximum emission wavelength of fluorescein. But the morphology and phase composition had no obvious alteration. Under fluorescence microscopy, the labeled nano-HAP powders., even after 24 h cell incubation, exhibited strong fluorescence.

  2. Nutrition marketing on food labels.

    Science.gov (United States)

    Colby, Sarah E; Johnson, LuAnn; Scheett, Angela; Hoverson, Bonita

    2010-01-01

    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. All items packaged with food labels (N = 56,900) in all 6 grocery stores in Grand Forks, ND were surveyed. Marketing strategy, nutrient label information, if the product was fruit/or milk based, and target age. Frequency distributions were computed. Forty-nine percent of all products contained nutrition marketing and of those, 48% had both nutrition marketing and were high in saturated fat, sodium and/or sugar (11%, 17%, and 31% respectively). Seventy-one percent of products marketed to children had nutrition marketing. Of those, 59% were high in saturated fat, sodium and/or sugar content, with more than half being high in sugar. The most commonly used nutrition marketing statements were "good source of calcium", "reduced/low/fat free", and "food company's health symbol". Nutrition marketing is commonly used on products high in saturated fat, sodium and/or sugar and is more often used on products marketed toward children than products marketed toward adults. Current food industry symbols may not be helping consumers select foods low in saturated fat, sodium or sugar. Published by Elsevier Inc.

  3. 78 FR 24211 - Draft Guidance for Industry on Safety Considerations for Container Labels and Carton Labeling...

    Science.gov (United States)

    2013-04-24

    ... Container Labels and Carton Labeling Design To Minimize Medication Errors; Availability AGENCY: Food and... the availability of a draft guidance for industry entitled ``Safety Considerations for Container... aspects of the container label and carton labeling design for prescription drug and biological...

  4. Stigma of a label: educational expectations for high school students labeled with learning disabilities.

    Science.gov (United States)

    Shifrer, Dara

    2013-01-01

    Poorer outcomes for youth labeled with learning disabilities (LDs) are often attributed to the student's own deficiencies or cumulative disadvantage; but the more troubling possibility is that special education placement limits rather than expands these students' opportunities. Labeling theory partially attributes the poorer outcomes of labeled persons to stigma related to labels. This study uses data on approximately 11,740 adolescents and their schools from the Education Longitudinal Survey of 2002 to determine if stigma influences teachers' and parents' educational expectations for students labeled with LDs and labeled adolescents' expectations for themselves. Supporting the predictions of labeling theory, teachers and parents are more likely to perceive disabilities in, and hold lower educational expectations for labeled adolescents than for similarly achieving and behaving adolescents not labeled with disabilities. The negative effect of being labeled with LDs on adolescents' educational expectations is partially mechanized through parents' and particularly teachers' lower expectations.

  5. Experimental and theoretical studies on the coordination chemistry of the N1-hexyl substituted pyrimidines (uracil, 5-fluorouracil and cytosine).

    Science.gov (United States)

    Barceló-Oliver, Miquel; Baquero, Beatriz Adriana; Bauzá, Antonio; García-Raso, Angel; Vich, Roberto; Mata, Ignasi; Molins, Elies; Terrón, Angel; Frontera, Antonio

    2013-06-01

    N(1)-Hexyl substituted pyrimidines were shown to present solubility properties closer to the real bases than the commonly used methyl and ethyl derivatives, yielding bi-layered structures in the solid state. The study of their coordination capabilities, mainly with Ag(I) and Hg(II), is presented in order to prove their reactivity. A series of coordination complexes, namely, [Hg(N(1)-hexyl-5-fluorouracilate)2]4·6H2O (1), (Ag(+))·[Ag(N(1)-hexyl-5-fluorouracilate)2](-) (2), [Ag(NO3)(N(1)-hexyluracil-κO(4))4] (3), [ZnBr2(N(1)-hexylcytosine)2] (4), [CdBr2(N(1)-hexylcytosine)2] (5), [HgBr2(N(1)-hexylcytosine)2] (6) and [CoBr2(N(1)-hexylcytosine)2] (7), have been synthesized in good yields and X-ray characterized. The presence of the hexyl chains and the fluorine atoms causes the formation of interesting 3D architectures in the solid state. Their structures have been further characterized by infrared spectra (IR) and elemental analyses. In addition, DFT-D3 calculations are used to study interesting noncovalent interactions observed in the solid state, like fluorine-fluorine, fluorine-π and hydrophobic interactions.

  6. Design and synthesis of some substituted thiazolo[3,2-a]pyrimidine derivatives of potential biological activities

    Directory of Open Access Journals (Sweden)

    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.

  7. Synthesis, X-ray characterization and computational studies of Cu(II) complexes of N-pyrazolyl pyrimidine.

    Science.gov (United States)

    Cañellas, Pablo; Bauzá, Antonio; García-Raso, Angel; Fiol, Juan J; Deyà, Pere M; Molins, Elies; Mata, Ignasi; Frontera, Antonio

    2012-08-28

    In this manuscript we report the synthesis and X-ray characterization of several complexes of Cu(II) with a 2-(1H-pyrazol-1-yl)-pyrimidine (L) ligand. Complexes CuLCl(2) (1), [CuL(2)(H(2)O)(2)](NO(3))(2) (2) and [CuL(2)H(2)O](NO(3))(2) (3) are mononuclear systems and [CuL(NO(3))(2)](n) (4) is polymeric. In the solid state, complexes 2 and 3 are characterized by the presence of anion-π interactions that are relevant for the final 3D architecture and packing. In complexes 1 and 4, where the counterion is directly bonded to the metal, anion-π interactions are not observed. High level ab initio calculations (RI-MP2/def2-TZVP) have been used to evaluate the noncovalent interactions observed in the solid state and the interplay between them. We also demonstrate that the presence of anions above the aromatic ligand is not due only to strong electrostatic interactions between the counterparts.

  8. A balanced pyrimidine pool is required for optimal Chk1 activation to prevent ultrafine anaphase bridge formation.

    Science.gov (United States)

    Gemble, Simon; Buhagiar-Labarchède, Géraldine; Onclercq-Delic, Rosine; Biard, Denis; Lambert, Sarah; Amor-Guéret, Mounira

    2016-08-15

    Cytidine deaminase (CDA) deficiency induces an excess of cellular dCTP, which reduces basal PARP-1 activity, thereby compromising complete DNA replication, leading to ultrafine anaphase bridge (UFB) formation. CDA dysfunction has pathological implications, notably in cancer and in Bloom syndrome. It remains unknown how reduced levels of PARP-1 activity and pyrimidine pool imbalance lead to the accumulation of unreplicated DNA during mitosis. We report that a decrease in PARP-1 activity in CDA-deficient cells impairs DNA-damage-induced Chk1 activation, and, thus, the downstream checkpoints. Chemical inhibition of the ATR-Chk1 pathway leads to UFB accumulation, and we found that this pathway was compromised in CDA-deficient cells. Our data demonstrate that ATR-Chk1 acts downstream from PARP-1, preventing the accumulation of unreplicated DNA in mitosis, and, thus, UFB formation. Finally, delaying entry into mitosis is sufficient to prevent UFB formation in both CDA-deficient and CDA-proficient cells, suggesting that both physiological and pathological UFBs are derived from unreplicated DNA. Our findings demonstrate an unsuspected requirement for a balanced nucleotide pool for optimal Chk1 activation both in unchallenged cells and in response to genotoxic stress.

  9. Severe Encephalopathy, Lactic Acidosis, Vegetative Instability and Neuropathy with 5-Fluorouracil Treatment – Pyrimidine Degradation Defect or Beriberi

    Directory of Open Access Journals (Sweden)

    A. Rosen

    2011-08-01

    Full Text Available We present the case of a 19-year-old female with nasopharyngeal carcinoma, who received two courses of chemotherapy with 5-fluorouracil (5-FU in combination with folic acid and cisplatin. Upon developing esophageal strictures in the course of her radiotherapy, she required total parenteral nutrition. In the course of therapy, the patient developed severe multisystem failure with encephalopathy, lactic acidosis, vegetative instability and neuropathy. The treatment with 5-FU can lead to severe toxicity due to enzyme deficiencies in the degradation of pyrimidines, but it can also lead to thiamine deficiency with the classic symptoms of beriberi. Beriberi is a rare disorder, usually attributed to malnutrition or alcoholism. 5-FU has been shown to induce thiamine depletion. Reduced food intake or total parenteral nutrition devoid of vitamin supplements may aggravate symptoms. We were unable to find a genetic cause for increased 5-FU toxicity in our patient, ruling out deficiencies of dihydropyrimidine dehydrogenase, dihydropyrimidinase or β-ureidopropionase and double-strand break repair deficits. We come to the conclusion that, even without any definable enzyme deficiency, treatment with 5-FU can lead to high toxicity due to thiamine deficiency if vitamin supplementation is not undertaken.

  10. Determining Chemical Reactivity Driving Biological Activity from SMILES Transformations: The Bonding Mechanism of Anti-HIV Pyrimidines

    Directory of Open Access Journals (Sweden)

    Mihai V. Putz

    2013-07-01

    Full Text Available Assessing the molecular mechanism of a chemical-biological interaction and bonding stands as the ultimate goal of any modern quantitative structure-activity relationship (QSAR study. To this end the present work employs the main chemical reactivity structural descriptors (electronegativity, chemical hardness, chemical power, electrophilicity to unfold the variational QSAR though their min-max correspondence principles as applied to the Simplified Molecular Input Line Entry System (SMILES transformation of selected uracil derivatives with anti-HIV potential with the aim of establishing the main stages whereby the given compounds may inhibit HIV infection. The bonding can be completely described by explicitly considering by means of basic indices and chemical reactivity principles two forms of SMILES structures of the pyrimidines, the Longest SMILES Molecular Chain (LoSMoC and the Branching SMILES (BraS, respectively, as the effective forms involved in the anti-HIV activity mechanism and according to the present work, also necessary intermediates in molecular pathways targeting/docking biological sites of interest.

  11. Crystal structure of (S-5,7-diphenyl-4,7-dihydrotetrazolo[1,5-a]pyrimidine

    Directory of Open Access Journals (Sweden)

    Ivy K. Price

    2015-04-01

    Full Text Available The title compound, C16H13N5, was synthesized by coupling aminotetrazole with chalcone in the presence of an amine organocatalyst derived from chincona alkaloid. There are two molecules, A and B, in the asymmetric unit. In molecule A, the dihedral angles between the partly hydrogenated pyrimidine ring system (r.m.s. deviation = 0.056 Å and the sp2- and sp3-bonded phenyl groups are 33.32 (11 and 86.53 (11°, respectively. The equivalent data for molecule B are 0.049 Å, and 27.05 (10 and 85.27 (11°, respectively. In the crystal, A+B dimers linked by pairs of N—H...N hydrogen bonds generate R22(8 loops. The dimers are linked by aromatic π–π stacking interactions [shortest centroid–centroid separation = 3.5367 (15 Å], which results in a three-dimensional network.

  12. Studies of antimicrobial activities of some 4-thiazolidinone fused pyrimidines, [1,5]-benzodiazepines and their oxygen substituted hydroxylamine derivatives

    Directory of Open Access Journals (Sweden)

    Singh Bhawani

    2010-01-01

    Full Text Available Thiazolidin-4-one fused pyrimidines, [1,5]-benzodiazepines and their oxygen substituted hydroxylamine derivatives have been screened for antibacterial, antifungal and antimalarial activity. Bacillus subtilis, Escherichia coli, Proteus mirabilis and Salmonella typhi were used for antibacterial screening. Aspergillus fumigatus and Candida albicans were used for antifungal screening and Plasmodium species were used for antimalarial screening. The antibacterial and antifungal activities are expressed in terms of zone of inhibition and antimalarial activity is expressed in IC 50 value. Fifteen compounds 2Xa, 2Xb, 2Xc, 2Xs, 3IV, 3Va, 3Vc, 3VIIIa, 3VIIIh, 3IXa, 3IXb, 3IXc, 3Xa, 4IXa and 4Xa were tested for antibacterial as well as antifungal activity and seven compounds 2IXb, 2Xb, 3VIIIc, 3Xc, 4IXa, 4Xa and 4IXw were tested for antimalarial activity. Streptomycin, griseofulvin and chloroquine were taken as standard drugs in antibacterial, antifungal and antimalarial activity, respectively. The compound 2Xs was found significant antimicrobial against Bacillus subtilis, E. coli, Aspergillus fumigatus and Candida albicans as well as compound 3Xa was significant antimicrobial against Bacillus subtilis, E. coli, Salmonella typhi, Aspergillus fumigatus and Candida albicans. The compound 2Xb showed significant antimalarial activity.

  13. Synthesis, Structure and Biological Activities of Novel Triazole Compounds Containing 4,6-Dimethyl-pyrimidin-2-ylthio Group

    Institute of Scientific and Technical Information of China (English)

    XU, Liang-Zhong(许良忠); JIAN, Fang-Fang(建方方); SHI, Jian-Gang(时建刚); LI, Lin(李琳)

    2004-01-01

    Four compounds were prepared by reacting 4,6-dimethyl-2-mercaptopyrimidine with α-bromo-α-(1,2,4-triazol-1-yl)-substituted acetylbenzene. Their structures were identified by means of elemental analysis, IR, and 1H NMR spectra. The single crystal structure of 2- [ 1 -(1,2,4-triazol- 1-yl)- 1-p-methoxyphenylcarbonylmethylthio] -4,6-dimethyl-pyrimidine was also determined. It crystallizes in monoclinic system, space group P21/c, a=0.8016(2) nm, b=1.2462(3) nm, c= 1.7824(4) nm,β=99.89(3)°, Z=4, V=1.7540(7) nm3, Dc=1.346 g/cm3, μ=0.205 mm-1, F(000)=744, final R1=0.0452. There is obviously potentially weak C-H…N intermolecular interaction between the molecules in the crystal lattice, which stabilizes the crystal structure. The result of the biological test showed that the four compounds all have some fungicidal and plant growth regulating activities.

  14. A QSAR study of integrase strand transfer inhibitors based on a large set of pyrimidine, pyrimidone, and pyridopyrazine carboxamide derivatives

    Science.gov (United States)

    de Campos, Luana Janaína; de Melo, Eduardo Borges

    2017-08-01

    In the present study, 199 compounds derived from pyrimidine, pyrimidone and pyridopyrazine carboxamides with inhibitory activity against HIV-1 integrase were modeled. Subsequently, a multivariate QSAR study was conducted with 54 molecules employed by Ordered Predictors Selection (OPS) and Partial Least Squares (PLS) for the selection of variables and model construction, respectively. Topological, electrotopological, geometric, and molecular descriptors were used. The selected real model was robust and free from chance correlation; in addition, it demonstrated favorable internal and external statistical quality. Once statistically validated, the training model was used to predict the activity of a second data set (n = 145). The root mean square deviation (RMSD) between observed and predicted values was 0.698. Although it is a value outside of the standards, only 15 (10.34%) of the samples exhibited higher residual values than 1 log unit, a result considered acceptable. Results of Williams and Euclidean applicability domains relative to the prediction showed that the predictions did not occur by extrapolation and that the model is representative of the chemical space of test compounds.

  15. Pyrimidine motif triple helix in the Kluyveromyces lactis telomerase RNA pseudoknot is essential for function in vivo.

    Science.gov (United States)

    Cash, Darian D; Cohen-Zontag, Osnat; Kim, Nak-Kyoon; Shefer, Kinneret; Brown, Yogev; Ulyanov, Nikolai B; Tzfati, Yehuda; Feigon, Juli

    2013-07-02

    Telomerase is a ribonucleoprotein complex that extends the 3' ends of linear chromosomes. The specialized telomerase reverse transcriptase requires a multidomain RNA (telomerase RNA, TER), which includes an integral RNA template and functionally important template-adjacent pseudoknot. The structure of the human TER pseudoknot revealed that the loops interact with the stems to form a triple helix shown to be important for activity in vitro. A similar triple helix has been predicted to form in diverse fungi TER pseudoknots. The solution NMR structure of the Kluyveromyces lactis pseudoknot, presented here, reveals that it contains a long pyrimidine motif triple helix with unexpected features that include three individual bulge nucleotides and a C(+)•G-C triple adjacent to a stem 2-loop 2 junction. Despite significant differences in sequence and base triples, the 3D shape of the human and K. lactis TER pseudoknots are remarkably similar. Analysis of the effects of nucleotide substitutions on cell growth and telomere lengths provides evidence that this conserved structure forms in endogenously assembled telomerase and is essential for telomerase function in vivo.

  16. Determining chemical reactivity driving biological activity from SMILES transformations: the bonding mechanism of anti-HIV pyrimidines.

    Science.gov (United States)

    Putz, Mihai V; Dudaş, Nicoleta A

    2013-07-30

    Assessing the molecular mechanism of a chemical-biological interaction and bonding stands as the ultimate goal of any modern quantitative structure-activity relationship (QSAR) study. To this end the present work employs the main chemical reactivity structural descriptors (electronegativity, chemical hardness, chemical power, electrophilicity) to unfold the variational QSAR though their min-max correspondence principles as applied to the Simplified Molecular Input Line Entry System (SMILES) transformation of selected uracil derivatives with anti-HIV potential with the aim of establishing the main stages whereby the given compounds may inhibit HIV infection. The bonding can be completely described by explicitly considering by means of basic indices and chemical reactivity principles two forms of SMILES structures of the pyrimidines, the Longest SMILES Molecular Chain (LoSMoC) and the Branching SMILES (BraS), respectively, as the effective forms involved in the anti-HIV activity mechanism and according to the present work, also necessary intermediates in molecular pathways targeting/docking biological sites of interest.

  17. Acidity constant and solvatochromic behavior of some pyrazolo[1,5-a]pyrimidin-2-amine derivatives

    Science.gov (United States)

    El-Gahami, Mohamed A.; Mekky, Ahmed E. M.; Saleh, Tamer S.; Al-Bogami, Abdullah S.

    2014-08-01

    The UV-visible electronic spectra of some azo compounds of pyrazolo[1,5-a]pyrimidin-2-amine have been studied. The solvatochromic behavior of these compounds was investigated by studying their spectra in pure organic solvents of different polarities such as cyclohexane carbon tetrachloride, chloroform, ethanol and DMF. These exhibits a red shift in its λmax with increase relative permittivity of medium changing from cyclohexane → carbon tetrachloride → chloroform → ethanol → DMF. The acid dissociation constants of these compounds were determined in aqueous-organic solvent mixtures such as acetone, methanol, ethanol and DMF. The ionization constants of the dyes in question depend largely on both the proportion and the nature of the organic solvent basicity contribute the major effects on the ionization process. In general, pKa values in all compounds decrease with increase relative permittivity of the medium. The acidity of studied azo compounds increases in the following order: p-NO2 < m-CF3 < p-F < p-Cl < p-H < p-CH3.

  18. Co3(RL)2(hfac)6 ladder complex of 5-[4-(N-tert-butyl-N-aminoxyl)phenyl]pyrimidine.

    Science.gov (United States)

    Field, Lora M; Morón, M Carmen; Lahti, Paul M; Palacio, Fernando; Paduan-Filho, Armando; Oliveira, Nei F

    2006-03-20

    5-[4-(N-tert-butyl-N-aminoxyl)phenyl]pyridimine (4NITPhPyrim = RL) forms a 1-D ladder polymer complex with Co(hfac)2 of stoichiometry Co3(RL)2(hfac)6, having antiparallel [Co(II)RL]n linear chains (rails) that are cross-linked by Pyrim-Co(hfac)2-Pyrim rungs. The magnetic behavior above 100 K is consistent with contributions from one high-spin Co(II) ion (the cross-link, S = 3/2) plus two Co-ON units with strongly antiferromagnetic (AFM) metal-radical exchange (each S = 1). The chiT data show an AFM downturn as the temperature drops. Assuming weak exchange along chain portions of the polymer due to poor spin polarization across the phenyl-pyrimidine bond in RL, a linear three-spin (S = 1, 3/2, and 1) fit to the T > 18 K data yields an AFM cross-linker (rung) effective exchange of J(CL)/k = (-)5.3 K = (-)3.7 cm(-)(1). Superexchange (sigma-orbital overlap) is a likely mechanism for the effective AFM exchange between CoON and Co spin sites in the three-spin groupings.

  19. An Optimal Labeling Scheme for Ancestry Queries

    CERN Document Server

    Fraigniaud, Pierre

    2009-01-01

    An ancestry labeling scheme assigns labels (bit strings) to the nodes of rooted trees such that ancestry queries between any two nodes in a tree can be answered merely by looking at their corresponding labels. The quality of an ancestry labeling scheme is measured by its label size, that is the maximal number of bits in a label of a tree node. In addition to its theoretical appeal, the design of efficient ancestry labeling schemes is motivated by applications in web search engines. For this purpose, even small improvements in the label size are important. In fact, the literature about this topic is interested in the exact label size rather than just its order of magnitude. As a result, following the proposal of a simple interval-based ancestry scheme with label size $2\\log_2 n$ bits (Kannan et al., STOC '88), a considerable amount of work was devoted to improve the bound on the size of a label. The current state of the art upper bound is $\\log_2 n + O(\\sqrt{\\log n})$ bits (Abiteboul et al., SODA '02) which is...

  20. Eye tracking and nutrition label use

    DEFF Research Database (Denmark)

    Graham, Dan J.; Orquin, Jacob Lund; Visschers, Vivianne H.M.

    2012-01-01

    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...... 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...... utilized eye tracking methodology, identifies directions for further research in this growing field, and makes research-based recommendations for ways in which labels could be modified to improve consumers’ ability to use nutrition labels to select healthful foods....