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Showing papers on "Xanthine published in 2011"


Journal ArticleDOI
TL;DR: The structures of a thermostabilized adenosine A(2A) receptor in complex with the xanthines xanthine amine congener and caffeine, as well as the A( 2A) selective inverse agonist ZM241385 are reported, providing new insight into the features that define the ligand binding pocket of theAdenosine receptor for ligands of diverse chemotypes aswell as the cytoplasmic regions that interact with signal transduction proteins.

497 citations


Journal ArticleDOI
TL;DR: It is demonstrated that bovine serum albumin (BSA) stabilized Au clusters exhibited highly intrinsic peroxidase-like activity and a sensitive and selective method forxanthine detection was developed using xanthine oxidase (XOD) and the as-prepared BSA-Au clusters.

304 citations


Journal ArticleDOI
TL;DR: The enzymatic route of purine ring catabolism has recently been completed by the discovery of several novel enzymes identified through comparative genome analyses as discussed by the authors, which has also emerged that catabolic intermediates, the ureides allantoin and allantoate, are likely to be involved in protecting plants against abiotic stress.

177 citations


Journal ArticleDOI
TL;DR: The compound 59 emerged as the most potent XO inhibitor (IC(50)=5.3 μM), and some of the important interactions of 59 with the amino acid residues of active site of XO have been figured out by molecular modeling.

96 citations


Journal ArticleDOI
TL;DR: In this article, the antioxidant potential of C. fistula seeds extract was evaluated by 2, 2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging assay and xanthine oxidase inhibition assay.
Abstract: This study investigates antioxidant activity of Cassia fistula seeds extract. The antioxidant potential of this extract was evaluated by 2, 2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging assay and xanthine oxidase inhibition assay. The IC50 values were calculated for DPPH and xanthine oxidase assays in order to evaluate the antioxidant efficiency of C. fistula seed extract. Total phenolic and flavonoid content were also determined. The seeds extract were exhibit antioxidant activity 59.587% with an IC50 value of 11.07 mg/ml in DPPH radical scavenging method. Furthermore, the C. fistula seeds extracts scavenged the superoxide radical generated by the xanthine/xanthine oxidase system. The percentage of xanthine oxidase inhibition activity of seed extract and allopurinol was 64.56 and 93.24%, respectively. The amount of total phenolic and flavonoid content was 474.25 ± 25.89 µg GAE/mg extract and 70.86 ± 1.43 µg catechin/mg extract respectively. High performance thin layer chromatography (HPTLC) screening indicates the presence of both free radical scavenging and phenolic compounds in C. fistula seed extract. The colored bands developed on TLC chromatogram visualized after spraying the plates with Folin-Ciocalteu’s and DPPH reagents which represent phenolic and radical scavenging compounds, respectively. Key words: Cassia fistula seed, antioxidant activity, xanthine oxidase inhibition, phenolic compounds.

90 citations


Journal ArticleDOI
TL;DR: The protein is of major interest as it is associated with ischemia reperfusion (I/R) injury, vascular disorders in diabetes, cardiovascular disorders, adipogenesis, metabolic syndrome, cancer, and many other disease conditions.
Abstract: Xanthine oxidoreductase (XOR) is a ubiquitous complex cytosolic molybdoflavoprotein which controls the rate limiting step of purine catabolism by converting xanthine to uric acid. It is known that optimum concentrations of uric acid (UA) and reactive oxygen species (ROS) are necessary for normal functioning of the body. The ability of XOR to perform detoxification reactions, and to synthesize UA and reactive oxygen species (ROS) makes it a versatile intra- and extra-cellular protective "housekeeping enzyme". It is also an important component of the innate immune system. The enzyme is a target of drugs against gout and hyperuricemia and the protein is of major interest as it is associated with ischemia reperfusion (I/R) injury, vascular disorders in diabetes, cardiovascular disorders, adipogenesis, metabolic syndrome, cancer, and many other disease conditions. Xanthine oxidoreductase in conjugation with antibodies has been shown to have an anti-tumor effect due to its ability to produce ROS, which in turn reduces the growth of cancer tissues. Apart from this, XOR in association with nitric oxide synthase also participates in myocardial excitation-contraction coupling. Although XOR was discovered over 100 years ago, its physiological and pathophysiological roles are still not clearly elucidated. In this review, various physiological and pathophysiological functional aspects of XOR and its association with various forms of cancer are discussed in detail.

79 citations


Journal ArticleDOI
TL;DR: The findings indicate that the metabolite I of erdosteine has antioxidant activity which, together with the drug's mucomodifying activity, may lead to a useful antiphlogistic effect.
Abstract: Acute and chronic lung diseases both lead to an extensive recruitment of neutrophils in the lungs. These cells play a major defensive role but, when activated, they are also an important source of reactive oxygen species, which generate a cytotoxic oxidant stress that triggers a self-sustaining phlogogenic loop. Erdosteine (CAS 84611-23-4) is a mucoactive drug whose metabolization leads to active metabolites with an SH group, and molecules bearing an SH group are also considered to have antioxidant activity. Luminol amplified chemiluminescence was used to investigate the oxidative bursts of human neutrophils and it was found that concentrations of 2.5, 5, 10 and 20 μg/ml of metabolite I of erdosteine significantly inhibit oxidative bursts in a concentration-related manner that overlaps the inhibition induced by the control drug N-acetylcysteine. Chemiluminescence was also studied in cell-free systems to see whether the drug also has direct scavenger activity, which was observed from 2.5 to 20 μg/ml of metabolite I using the xanthine/xanthine oxidase assay and at concentrations of 0.039 to ≥ 2.5 μg/ml using the highly-sensitive hypochlorous acid/H2O2 assay. The findings indicate that the metabolite I of erdosteine has antioxidant activity which, together with the drug’s mucomodifying activity, may lead to a useful antiphlogistic effect.

76 citations


Journal ArticleDOI
Hua Li1, Zhiying Yan1, Jian Zhu1, Jing Yang1, Jianshe He1 
TL;DR: In vivo evidence is provided that resveratrol could exert neuroprotective effect against ischemia injury by improving brain energy metabolism and alleviating oxidative stress via inhibiting xanthine oxidase activity and preventing the production of hypoxanthine,xanthine and oxygen radicals during ischemIA/reperfusion.

70 citations


Journal ArticleDOI
TL;DR: In this article, the contribution and functional significance of the xanthine oxidase enzyme as a potential source of oxidant production in aged skeletal muscle during repetitive in situ electrically stimulated isometric contractions was examined.

70 citations


Journal ArticleDOI
TL;DR: These data confirm previous findings that exposure to intermittent hypoxia impairs endothelium-dependent vasodilation in skeletal muscle resistance arteries and extend them by demonstrating that this impairment can be prevented with allopurinol.
Abstract: Background: Xanthine oxidase is a major source of superoxide in the vascular endothelium Previous work in humans demonstrated improved conduit artery function following xanthine ox

62 citations


Journal ArticleDOI
TL;DR: Cerebrospinal fluid concentrations of homovanillic acid and the purine compound xanthine and the ratio differed as a function of disease severity, as measured by the sum of Unified Parkinson's Disease Rating Scale Activities of Daily Living and Motor Exam ratings, adding to other neurochemical evidence that links purine metabolism to Parkinson's disease.

Journal ArticleDOI
TL;DR: Ndm was deduced to be a Rieske [2Fe-2S]-domain-containing non-haem iron oxygenase based on its distinct absorption spectrum and significant identity of the N-terminal sequences of NdmA and NdmB with the gene product of an uncharacterized caffeine demethylase in P. putida IF-3 and a hypothetical protein in Janthinobacterium sp.
Abstract: N-Demethylation of many xenobiotics and naturally occurring purine alkaloids such as caffeine and theobromine is primarily catalysed in higher organisms, ranging from fungi to mammals, by the well-studied membrane-associated cytochrome P450s. In contrast, there is no well-characterized enzyme for N-demethylation of purine alkaloids from bacteria, despite several reports on their utilization as sole source of carbon and nitrogen. Here, we provide what we believe to be the first detailed characterization of a purified N-demethylase from Pseudomonas putida CBB5. The soluble N-demethylase holoenzyme is composed of two components, a reductase component with cytochrome c reductase activity (Ccr) and a two-subunit N-demethylase component (Ndm). Ndm, with a native molecular mass of 240 kDa, is composed of NdmA (40 kDa) and NdmB (35 kDa). Ccr transfers reducing equivalents from NAD(P)H to Ndm, which catalyses an oxygen-dependent N-demethylation of methylxanthines to xanthine, formaldehyde and water. Paraxanthine and 7-methylxanthine were determined to be the best substrates, with apparent K m and kcat values of 50.4±6.8 μM and 16.2±0.6 min−1, and 63.8±7.5 μM and 94.8±3.0 min−1, respectively. Ndm also displayed activity towards caffeine, theobromine, theophylline and 3-methylxanthine, all of which are growth substrates for this organism. Ndm was deduced to be a Rieske [2Fe–2S]-domain-containing non-haem iron oxygenase based on (i) its distinct absorption spectrum and (ii) significant identity of the N-terminal sequences of NdmA and NdmB with the gene product of an uncharacterized caffeine demethylase in P. putida IF-3 and a hypothetical protein in Janthinobacterium sp. Marseille, both predicted to be Rieske non-haem iron oxygenases.

Journal ArticleDOI
R F Bruns1, J H Fergus1
TL;DR: From literature data on functional activity, it is apparent that useful adenosine antagonist activity in‐vivo is only seen in compounds with solubility/affinity ratios greater than 100.
Abstract: The practical use of many adenosine receptor antagonists is limited by poor aqueous solubility. In some cases, solubilities are so low that they are difficult to measure by conventional means. To determine solubilities of adenosine antagonists, a sensitive radioreceptor method has been developed. Solubilities in Tris buffer (pH 7.7) ranged from 141 nM for 8-(2-amino-4-chlorophenyl)-1,3-dipropylxanthine to 945 microM for the amino-substituted xanthine PD 113,297. Ratios between solubility and adenosine receptor affinity varied from 15.8 for the A2-selective antagonist HTQZ to 169,000 for PD 113,297. From literature data on functional activity, it is apparent that useful adenosine antagonist activity in-vivo is only seen in compounds with solubility/affinity ratios greater than 100.

Journal ArticleDOI
TL;DR: The synthesis of a series of pyrimidin-5-one analogues as effective and a new class of xanthine oxidase inhibitors that have potential to be more efficacious than allopurinol to treat gout and possibly against cardiovascular diseases are reported.

Journal ArticleDOI
TL;DR: A commercial xanthine oxidase (XOD) was immobilized covalently onto carboxylated multiwalled carbon nanotubes (c-MWCNT) and polyaniline (PANI) composite film electrodeposited on the surface of a Pt electrode, using N-ethyl-N′-(3-dimethyl aminopropyl) carbodiimide (EDC) and N-hydroxy succinimides (NHS) chemistry as discussed by the authors.

Journal ArticleDOI
TL;DR: In vivo, intragastric administration of Compound 1 was able to significantly reduce serum uric acid levels and inhibited hepatic xanthine oxidase activities of hyperuricemic mice in a dose-dependent manner and these results suggest thatcompound 1 is a novel competitive xanthines oxidase inhibitor and is worthy of further development.

Journal ArticleDOI
TL;DR: A new molecularly imprinted polymer was synthesized using ofloxacin and theophylline as template and methacryclic acid as function monomer and it was employed as a special dispersant of matrix solid-phase dispersion for selective extraction of fluoroquinolones and xanthine derivatives from human serum samples.

Journal ArticleDOI
TL;DR: The integrity of DNA purine bases was used to evaluate the antioxidant capacity of DNA-based antioxidant sensors and the damaging agent chosen was the O 2 - radical enzymatically generated by the xanthine/xanthine oxidase system.

Journal ArticleDOI
TL;DR: All the extracts, particularly the total oligomers flavonoids (TOF) extract significantly decreased the genotoxicity induced by aflatoxin B(1) and nitrofurantoin, and the potential of T. ramosissimum to prevent mutations and also its antioxidant effect is emphasized.

Journal ArticleDOI
TL;DR: This is the first systematic probing of a potent AR antagonist tethered on a dendrimer and its activity as a function of variable loading.

Journal ArticleDOI
TL;DR: Molecular modeling studies were performed to gain an insight into its binding mode with xanthine oxidase, and to provide the basis for further structure-guided design of new non-purine xanthines oxidase inhibitors associated with the xanthone framework.

Journal ArticleDOI
TL;DR: Relatively strong π–π interaction energies between caffeine and the intercalators were found, suggesting an “interceptor” role of caffeine protecting the DNA from intercalation.
Abstract: Many anti-tumor drugs function by intercalating into DNA. The xanthine alkaloid caffeine can also intercalate into DNA as well as form π-π molecular complexes with other planar alkaloids and anti-tumor drugs. The presence of caffeine could interfere with the intercalating anti-tumor drug by forming π-π molecular complexes with the drug, thereby blocking the planar aromatic drugs from intercalating into the DNA and ultimately lowering the toxicity of the drug to the cancer cells. The cytotoxic activities of several known DNA intercalators (berberine, camptothecin, chelerythrine, doxorubicin, ellipticine, and sanguinarine) on MCF-7 breast cancer cells, both with and without caffeine present (200 μg/mL) were determined. Significant attenuation of the cytotoxicities by caffeine was found. Computational molecular modeling studies involving the intercalating anti-tumor drugs with caffeine were also carried out using density functional theory (DFT) and the recently developed M06 functional. Relatively strong π-π interaction energies between caffeine and the intercalators were found, suggesting an "interceptor" role of caffeine protecting the DNA from intercalation.

Journal ArticleDOI
TL;DR: IP6 significantly reduced glucose level, HbA1C, lipid profile and lipid peroxidation, and increased body weight, high density lipoprotein level and antioxidant status in liver and small intestine, indicating that IP6 possess promising in vitro and in vivo antidiabetic activity.
Abstract: Phytic acid, inositol hexaphosphate (IP6) a natural plant constituent and antioxidant exhibits protective action in carcinogenesis, Alzheimer's, hypercholesterolemia, diabetes and inflammations when taken in diet. The aim of this study is to evaluate effect of phytic acid in streptozotocin (STZ)-nicotinamide-induced type 2 diabetes in rats. The STZ-nicotinamide induced diabetic rats were orally treated with vehicle (2%w/v Tween 80), glimepiride (2.5 mg/kg) and IP6 (650 mg/kg) for 28 days. The blood glucose level, body weight, glycosylated haemoglobin (HbA1C), lipid profile, lipid peroxidation, antioxidant status (liver and small intestine) was measured and compared with control. Xanthine dehydrogenase (XDH) and xanthine (XO) activity was measured in small intestine of diabetic rats. In vitro inhibition of carbohydrate digestive enzymes (α-glucosidase and α-amylase) was also determined. IP6, significantly (P<0.01) reduced glucose level, HbA1C, lipid profile and lipid peroxidation, and increased body weight, high density lipoprotein level and antioxidant status in liver and small intestine. Decrease in XO and increase in XDH activity was observed in treatment groups compared to diabetic control. Dose dependent inhibition of α-glucosidase and (α-amylase activity was observed for phytic acid when compared to standard drug acarbose. These results clearly indicate that IP6 possess promising in vitro and in vivo antidiabetic activity.

Journal ArticleDOI
TL;DR: The cancer chemopreventive properties and cytotoxic activities of the isolated compounds were evaluated in this paper, where they showed excellent antioxidant activity in the oxygen radical absorbance capacity (ORAC) assay with 12.8-24.9 ORAC units.

Journal ArticleDOI
TL;DR: The results demonstrated that the DNA-based biosensor is suitable for the rapid assess of TAC in beverages.

Journal Article
TL;DR: In this paper, the authors describe the analyses of theobromine-related compounds by reversed phase high-performance liquid chromatography with ultraviolet detection (UV) in four sources: food, beverages, biological fluids and plants.
Abstract: Summary Theobromine and its related compounds, such as caffeine and theophylline, are secondary metabolites that belong to the alkaloids and have economic and cultural importance. These alkaloids have demonstrated stimulatory effects on the central nervous, gastrointestinal, cardiovascular, renal and respiratory systems, resulting in 'energy arousal', increased motivation to work, increased alertness and increased cognitive function. Several analytical methods have been used to analyse these compounds, but reversed phase high-performance liquid chromatography (RP-HPLC) is the most commonly applied because of its efficiency, sensitivity, specificity and speed. This review describes the analyses of theobromine-related compounds by RP-HPLC with ultraviolet detection (UV) in four sources: food, beverages, biological fluids and plants. Many RP-HPLC methods have been developed and optimized for the detection and quantification of these natural compounds. Elution under isocratic conditions is the most frequent method, with a water, methanol and acetonitrile mixture modified with acetic, phosphoric or formic acid as the mobile phase. For xanthine analysis, the use of reversed phase high-performance liquid chromatography with an ultraviolet/diode array detector (UV/DAD) is particularly suitable as derivation is not required; it allows the analysis of absorbance at all wavelengths, it is simple and rapid.

Journal ArticleDOI
TL;DR: Isocratic reverse‐phase high performance liquid chromatography techniques were developed to resolve and quantitate the purine nucleosides adenosine and inosine and their metabolites hypoxanthine, xanthine and uric acid in the cerebrospinal fluid of the rat.
Abstract: Isocratic reverse-phase high performance liquid chromatography techniques were developed to resolve and quantitate the purine nucleosides adenosine (Ado) and inosine (Ino) and their metabolites hypoxanthine (Hyp), xanthine (Xan), and uric acid (UA) in the cerebrospinal fluid of the rat. The moving phase composition for resolving hypoxanthine, xanthine and uric acid was a 0.22 M, pH 5.8 phosphate buffer. The moving phase composition for resolving adenosine and inosine was a 0.22 M, pH 6.8 phosphate buffer, 7% methanol (v/v) and 2.5 mM tetrabutylammonium phosphate. The observed cerebrospinal fluid concentrations in the rat were: Ado = 35 +/- 9 nM (s.e.m.), Ino = 359 +/- 85 nM, Hyp = 243 +/- 77 nM, Xan = 1340 +/- 423 nM and UA = 6130 +/- 678 nM.

Journal ArticleDOI
TL;DR: Norway lobster Nephrops norvegicus has purineolytic capacity and, under prolonged hypoxia, produces purines de novo as an ammonia-detoxification strategy that has probable survival value for a benthic burrowing species that may experience periods of severe Hypoxia.
Abstract: Under prolonged (>24 h) emersion, Norway lobster Nephrops norvegicus changed purineolytic pathways in response to increased levels of circulating ammonia. Haemolymph levels of urea and uric acid more than doubled during emersion, but xanthine oxidase was not detected, even after 72 h emersion. Xanthine dehydrogenase (XDH) was the only form of xanthine oxidoreductase detected, so the metabolic costs of producing uric acid would have been relatively small. Although ammonia, urea, uric acid and XDH all accumulated in the haemolymph during emersion, the relative proportions of ammonia and urea stayed the same at all times, which suggests the presence of enzymes from the uricolyic pathway (e.g. uricase and urease). Supranormal ammonia effluxes occurred almost immediately following re-immersion in amounts that indicate a high degree of hypoxia tolerance under emersion and that this is negatively related with the prevailing temperature. We conclude that N. norvegicus has purineolytic capacity and, under prolonged hypoxia, produces purines de novo as an ammonia-detoxification strategy that has probable survival value for a benthic burrowing species that may experience periods of severe hypoxia.

Journal ArticleDOI
TL;DR: In this article, a novel xanthine biosensors were successfully fabricated by immobilizing xanthines oxidase on polyvinylferrocenium perchlorate matrix (PVF+ClO4−) and platinum electrodeposited polyvinyl alcohol (PVB) matrix.
Abstract: Novel xanthine biosensors were successfully fabricated by immobilizing xanthine oxidase on polyvinylferrocenium perchlorate matrix (PVF+ClO4−) and platinum electrodeposited polyvinylferrocenium perchlorate matrix. PVF+ClO4− film was coated on Pt electrode at +0.7 V vs. Ag/AgCl by electrooxidation of polyvinylferrocene (PVF). Platinum nanoparticles were deposited on PVF+ClO4− electrode by electrochemical deposition in 2.0 mM H2PtCl6 solution at −0.2 V. Xanthine oxidase was incorporated into the polymer matrix via ion exchange process by immersing modified Pt electrodes in the enzyme solution. The amperometric responses of the biosensors were measured via monitoring oxidation current of hydrogen peroxide at +0.5 V. Under the optimal conditions, the linear ranges of xanthine detection were determined as 1.73 × 10−3–1.74 mM for PVF+XO− and 0.43 × 10−3–2.84 mM for PVF+XO−/Pt. The detection limits of xanthine were 5.20 × 10−4 mM for PVF+XO− and 1.30 × 10−4 mM for PVF+XO−/Pt. Moreover, the effects of applied potential, electrodeposition potential, H2PtCl6 concentration, amount of electrodeposited Pt nanoparticles, thickness of polymeric film, temperature, immobilization time, xanthine and xanthine oxidase concentrations on the response currents of the biosensors were investigated in detail. The effects of interferents, the operational and storage stabilities of biosensors and the applicabilities to drug samples of the biosensors analysis were also evaluated.

Journal ArticleDOI
18 May 2011-PLOS ONE
TL;DR: The transcriptome data analysis revealed that low oxygen supply has three major effects on metabolism: enhance carbon metabolism, inhibit degradation of nitrogen sources (glutamate family amino acids and xanthine) and purine synthesis, which provide new insights into the relationship between oxygen supply and metabolism.
Abstract: Dissolved oxygen (DO) is an important factor for adenosine fermentation. Our previous experiments have shown that low oxygen supply in the growth period was optimal for high adenosine yield. Herein, to better understand the link between oxygen supply and adenosine productivity in B. subtilis (ATCC21616), we sought to systematically explore the effect of DO on genetic regulation and metabolism through transcriptome analysis. The microarrays representing 4,106 genes were used to study temporal transcript profiles of B. subtilis fermentation in response to high oxygen supply (agitation 700 r/min) and low oxygen supply (agitation 450 r/min). The transcriptome data analysis revealed that low oxygen supply has three major effects on metabolism: enhance carbon metabolism (glucose metabolism, pyruvate metabolism and carbon overflow), inhibit degradation of nitrogen sources (glutamate family amino acids and xanthine) and purine synthesis. Inhibition of xanthine degradation was the reason that low oxygen supply enhanced adenosine production. These provide us with potential targets, which can be modified to achieve higher adenosine yield. Expression of genes involved in energy, cell type differentiation, protein synthesis was also influenced by oxygen supply. These results provided new insights into the relationship between oxygen supply and metabolism.