pyrimidinones and pyrimidin-2-one-beta-ribofuranoside

pyrimidinones has been researched along with pyrimidin-2-one-beta-ribofuranoside* in 5 studies

Other Studies

5 other study(ies) available for pyrimidinones and pyrimidin-2-one-beta-ribofuranoside

ArticleYear
Pyrimidinone: versatile Trojan horse in DNA photodamage?
    Photochemical & photobiological sciences : Official journal of the European Photochemistry Association and the European Society for Photobiology, 2015, Sep-26, Volume: 14, Issue:9

    (6-4) Photolesions between adjacent pyrimidine DNA bases are prone to secondary photochemistry. It has been shown that singlet excited (6-4) moieties form Dewar valence isomers as well as triplet excitations. We here report on the triplet state of a minimal model for the (6-4) photolesion, 1-methyl-2(1H)-pyrimidinone. Emphasis is laid on its ability to abstract hydrogen atoms from alcohols and carbohydrates. Steady-state and time-resolved experiments consistently yield bimolecular rate constants of ∼10(4) M(-1) s(-1) for the hydrogen abstraction. The process also occurs intramolecularly as experiments on zebularine (1-(β-d-ribofuranosyl)-2(1H)-pyrimidinone) show.

    Topics: Cytidine; DNA; DNA Damage; Hydrogen; Light; Methanol; Molecular Structure; Photochemical Processes; Pyrimidinones; Spectrum Analysis; Water

2015
Methylation of zebularine investigated using density functional theory calculations.
    Journal of computational chemistry, 2011, Jul-30, Volume: 32, Issue:10

    Deoxyribonucleic acid (DNA) methylation is an epigenetic phenomenon, which adds methyl groups into DNA. This study reveals methylation of a nucleoside antibiotic drug 1-(β-D-ribofuranosyl)-2-pyrimidinone (zebularine or zeb) with respect to its methylated analog, 1-(β-D-ribofuranosyl)-5-methyl-2-pyrimidinone (d5) using density functional theory calculations in valence electronic space. Very similar infrared spectra suggest that zeb and d5 do not differ by types of the chemical bonds, but distinctly different Raman spectra of the nucleoside pair reveal that the impact caused by methylation of zeb can be significant. Further valence orbital-based information details on valence electronic structural changes caused by methylation of zebularine. Frontier orbitals in momentum space and position space of the molecules respond differently to methylation. Based on the additional methyl electron density concentration in d5, orbitals affected by the methyl moiety are classified into primary and secondary contributors. Primary methyl contributions include MO8 (57a), MO18 (47a), and MO37 (28a) of d5, which concentrates on methyl and the base moieties, suggest certain connection to their Frontier orbitals. The primary and secondary methyl affected orbitals provide useful information on chemical bonding mechanism of the methylation in zebularine.

    Topics: Cytidine; Methylation; Molecular Dynamics Simulation; Pyrimidinones; Spectrum Analysis, Raman

2011
Antitumor properties of 2(1H)-pyrimidinone riboside (zebularine) and its fluorinated analogues.
    Journal of medicinal chemistry, 1991, Volume: 34, Issue:11

    2(1H)-Pyrimidinone riboside (zebularine, 1b) and its 5-fluoro (6b) and 2'-ara-fluoro (7b) analogues have been synthesized and evaluated in vivo as antitumor agents. Zebularine provides increase in life span (ILS) values of ca. 70% against intraperitoneal (ip) murine B16 melanoma and 50% against P388 leukemia. This compound is active when administered either ip or orally against ip or subcutaneously implanted L1210 leukemia, producing ILS values of about 100% at an optimum dose of 400 mg/kg. 1b is also active (60% ILS) against ara-C-resistant L1210. The analogous unsubstituted purine riboside nebularine (2) has modest activity against P388 leukemia (60% ILS). While 2'-ara-fluorozebularine (7b) is only marginally active (40% ILS) at high doses against L1210 leukemia, 5-fluoro analogue 6b is more active than zebularine and is ca. 100 times more potent. Although the activity of 6b is about the same as that of 1b against P388 leukemia, greater potency also is realized in this model. Zebularine is a strong inhibitor of cytidine deaminase, but in contrast to tetrahydrouridine, 1b is acid-stable. In an attempt to use this property to advantage in oral administration, 1b and ara-C have been orally coadministered to mice with ip L1210 leukemia. When zebularine is given in divided doses, up to a 2-fold increase in activity is realized, relative to treatment with the same dose of ara-C alone.

    Topics: Administration, Oral; Animals; Antineoplastic Agents; Arabinonucleosides; Cytidine; Drug Screening Assays, Antitumor; Injections, Intraperitoneal; Injections, Subcutaneous; Leukemia L1210; Leukemia P388; Mice; Pyrimidine Nucleosides; Pyrimidinones; Structure-Activity Relationship

1991
Binding of pyrimidin-2-one ribonucleoside by cytidine deaminase as the transition-state analogue 3,4-dihydrouridine and the contribution of the 4-hydroxyl group to its binding affinity.
    Biochemistry, 1989, Nov-28, Volume: 28, Issue:24

    Cytidine deaminase, purified to homogeneity from constitutive mutants of Escherichia coli, was found to bind the competitive inhibitors pyrimidin-2-one ribonucleoside (apparent Ki = 3.6 x 10(-7) M) and 5-fluoropyrimidin-2-one ribonucleoside (apparent Ki = 3.5 x 10(-8) M). Enzyme binding resulted in a change of the lambda max of pyrimidin-2-one ribonucleoside from 303 nm for the free species to 239 nm for the bound species. The value for the bound species was identical with that of an oxygen adduct formed by combination of hydroxide ion with 1,3-dimethyl-2-oxopyrimidinium (239 nm), but lower than that of a sulfur adduct formed by combination of the thiolate anion of N-acetylcysteamine with 1,3-dimethyl-2-oxopyrimidinium (259 nm). The results suggest that pyrimidin-2-one ribonucleoside is bound by cytidine deaminase as an oxygen adduct, probably the covalent hydrate 3,4-dihydrouridine, rather than intact or as an adduct involving a thiol group of the enzyme. In dilute solution at 25 degrees C, the equilibrium constant for formation of a single diastereomer of 3,4-dihydrouridine from pyrimidin-2-one ribonucleoside was estimated as approximately 4.7 x 10(-6), from equilibria of dissociation of water, protonation of 1-methylpyrimidin-2-one, and combination of the 1,3-dimethylpyrimidinium cation with the hydroxide ion.(ABSTRACT TRUNCATED AT 250 WORDS)

    Topics: Cytidine; Cytidine Deaminase; Electrophoresis, Polyacrylamide Gel; Escherichia coli; Molecular Structure; Nucleoside Deaminases; Pyrimidine Nucleosides; Pyrimidinones; Ribonucleosides; Spectrophotometry, Ultraviolet; Thermodynamics; Uridine

1989
The mechanism of inhibition of DNA synthesis in Escherichia coli by pyrimidin-2-one beta-D-ribofuranoside.
    Biochimica et biophysica acta, 1973, Sep-28, Volume: 324, Issue:1

    Topics: Animals; Biological Transport; Carbon Radioisotopes; Cattle; Chromatography, Paper; Cytidine; Deoxyribonucleosides; Deoxyribonucleotides; DNA, Bacterial; Electrophoresis, Paper; Escherichia coli; Kinetics; Methyltransferases; Mutation; Pentosyltransferases; Pyrimidine Nucleosides; Pyrimidinones; Ribonucleosides; Thymidylate Synthase; Thymus Gland; Time Factors

1973