5614-64-2Relevant articles and documents
Quantitation of 8-oxoguanine and strand breaks produced by four oxidizing agents
Kennedy, Laura J.,Moore Jr., Kenneth,Caulfield, Jennifer L.,Tannenbaum, Steven R.,Dedon, Peter C.
, p. 386 - 392 (1997)
Reactive oxygen species, produced endogenously or by exposure to environmental chemicals and ionizing radiation, induce a wide range of DNA lesions. The variety of chemistries associated with different oxidants suggests that each will produce a unique spectrum of DNA damage products. To extend our efforts to relate genotoxin chemistry to DNA damage, we measured both strand breaks and 8-oxoguanine (8-oxoG) in DNA after exposure to γ- radiation, Fe(II)-EDTA/H2O2, Cu(II)/H2O2, and peroxynitrite at concentrations approaching physiological relevance. We found that the ratio of 8-oxoG to strand breaks varied more than 10-fold depending on the oxidizing agent: ~0.4 for Cu(II)/H2O2 and peroxynitrite and ~0.03 for Fe(II)-EDTA/H2O2 and γ-radiation. In the case of Cu(II)/H2O2, the relative proportion of 8-oxoG and strand breaks was found to vary more than 2-fold (0.14-0.37) for different Cu(II) concentrations, consistent with other studies. We were able to detect 8-oxoG formation by peroxynitrite by using low peroxynitrite concentrations in conjunction with a sensitive immunoaffinity/HPLC-ECD methodology. The level of 8-oxoG relative to strand breaks produced by peroxynitrite was higher than that produced by Fe(II)- EDTA/H2O2 and γ-radiation, which is consistent with the altered reactivity or accessibility of a non-hydroxyl radical species produced by peroxynitrite.
Photooxidative damage of guanine in DG and DNA by the radicals derived from the α cleavage of the electronically excited carbonyl products generated in the thermolysis of alkoxymethyl-substituted dioxetanes and the photolysis of alkoxyacetones
Adam,Arnold,Saha-Moeller
, p. 597 - 604 (2001)
On thermolysis of the methoxy (MeO-TMD), tert-butoxy (tBuO-TMD), and hydroxy (HO-TMD) derivatives of 3,3,4,4-tetramethyl-1,2-dioxetane (TMD) in the presence of dG and calf-thymus DNA, the guanine is oxidized considerably more efficiently than the parent TMD. The same trend in the oxidative reactivity is observed for the photolysis of the corresponding oxy-substituted ketones versus acetone. The oxidative reactivity order in the dioxetane thermolysis, as well as in the ketone photolysis, parallels the ability of the excited ketones to release radicals (determined by spin trapping with DMPO and EPR spectroscopy) upon α cleavage (Norrish-type-I reaction). In the presence of molecular oxygen, the carbon-centered radicals are scavenged to produce peroxyl radicals, which are proposed as the reactive species in the, oxidation of the guanine in dG and calf-thymus DNA.
HETEROCYCLIC GTP CYCLOHYDROLASE 1 INHIBITORS FOR THE TREATMENT OF PAIN
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Page/Page column 68, (2011/04/19)
The present invention relates to the field of small molecule heterocyclic inhibitors of GTP cyclohydrolase (GCH-I), or a tautomer, prodrug, or pharmaceutically acceptable salt thereof. The invention also features pharmaceutical compositions of the compounds and the medical use of these compounds for the treatment or prevention of pain (e.g., inflammatory pain, nociceptive pain, functional pain, or neuropathic pain).
Photooxidation of substituted purines in presence of peroxydisulphate in aqueous solution
Swaraga, Midudhula Sudha,Adinarayana, Mundra
, p. 2096 - 2100 (2007/10/03)
Photooxidation of purine bases, viz., caffeine, theobromine, theophylline, xanthine, hypoxanthine, adenine and guanine in aqueous solution has been carried out in presence of peroxydisulphate (PDS). Peroxydisulphate is activated to SO4.- at 254 nm. The reactions are followed by measuring the absorbance of purine bases at their respective γmax]. The rates of reactions are calculated under different experimental conditions. The light intensity is measured using peroxydisulphate solution as standard chemical actinometer. Using reaction rate and light intensity at 254 nm, the quantum yields are calculated. The rates of photooxidation of purine bases are found to increase with increase in [PDS] and independent of [purine]. The increase of light intensity has been found to increase the rate of oxidation. The quantum yields are found to depend on [purine] but independent of [PDS] and light intensity. On the basis of experimental results a probable mechanism is suggested in which peroxydisulphate on photolysis gives sulphate radical anion which initiates the reaction by capturing an electron from C8 position of purine to form purine radical cation. This radical cation deprotonates and undergoes further oxidation to give C(8) hydroxy purine.
