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Xanthine Derivatives (xanthine + derivative)

Distribution by Scientific Domains
Chemistry60%
Medical Sciences40%

Selected Abstracts

The effects of pentoxifylline on liver regeneration after portal vein ligation in rats

LIVER INTERNATIONAL, Issue 2 2007
Uzer Kucuktulu
Abstract Aim: To determine the effects of pentoxifylline, a methyl xanthine derivative on hepatic cell production of uninterferred lobe after portal vein branch ligation. Methods: Sixty-six rats were randomly allocated into 9 groups with 8 rats in PVL groups and 6 rats in sham operation groups. The portal branches of the median and the lateral liver lobes, corresponding to approximately 70% of the liver voluma were ligated in the PVL groups. The control group received 0.9% NaCl solution. The rats in the treatment groups received pentoxypilline at the dose of 50 mg/kg/dy. After 1,2,4 days of portal vein ligation in both PVL and PVNL lobes the levels of adenine nucleotides were determined and flowcytometric analysis of cell cycles were performed. Results: On the first day of portal branch ligation energy charge was significantly lower, in pentoxifylline treated group comparing to pentoxfylline untreated group, both in PVL and PVNL lobes (P<0.05). Proliferative indexes were 0.38 and 0.29 in pentoxifylline treated and pentoxifylline untreated PVNL lobes respectively (P<0.05). Conclusion: Pentoxifylline treatment resulted in an increase of percentage of calls entering mitosis phase on the first day after PVL, somehow accelerating the regenaration process. [source]

Predictive 3D-Quantitative Structure-Activity Relationship for A1 and A2A Adenosine Receptor Ligands

MOLECULAR INFORMATICS, Issue 11-12 2009
Olga Yuzlenko
Abstract The use of QSAR applications to develop adenosine receptor (AR) antagonists is not so common. A library of all xanthine derivatives, obtained at the Department of Technology and Biotechnology of Drugs, was created. Sixty-three active adenosine A1 receptor ligands and one hundred thirty nine active adenosine A2A receptor ligands were used for 3D-QSAR investigation. The 3D-QSAR equations with a high predictive power in estimating the binding affinity values of potential A1 and A2A ARs ligands were derived. For the first time, hybrid shape-property descriptors were used in 3D-QSAR for xanthine ARs ligands. The obtained models were characterized by a high regression and cross-validation coefficients. Two types of the model validation were tested , dividing the library into the training set for model development and external set for model validation and increasing the number of library components and checking the model by cross-validated regression coefficient. The analysis of the results depicts that for the A1 AR binding activity it is important for ligands to possess R1 -propyl substituents along with the phenyl or benzyl substituents bearing halogen atom and phenethyl moiety. For A2A AR affinity it could be favorable to introduce phenethyl or phenyl substituent connected with the tricyclic ring by the alkoxy chain. The nature of R1 group may not significantly affect the A2A AR affinity. High predictive power of the equations suggests their use for further development of adenosine receptor antagonists within xanthine derivatives. [source]

Electrospray ionization mass spectrometric characterization and quantitation of xanthine derivatives using isotopically labelled analogues: an application for equine doping control analysis

RAPID COMMUNICATIONS IN MASS SPECTROMETRY, Issue 14 2004
Mario Thevis
Isotope-dilution mass spectrometry has been employed successfully in numerous fields of analytical chemistry enabling the establishment of fast and reliable procedures. In equine sports, xanthine derivatives such as caffeine and theobromine are prohibited, and doping control laboratories analyze horse urine specimens regarding these illicit performance-enhancing drugs. Theobromine has to exceed a threshold level of 2,,g/mL, hence a robust and reliable quantitation is required. Stably deuterated theobromine and caffeine were synthesized by the reaction of xanthine or theobromine with iodomethane-d3 in the presence of N -methyl- N -trimethylsilyltrifluoroacetamide or potassium carbonate in acetonitrile, respectively. Both compounds were characterized by nuclear magnetic resonance spectroscopy and electrospray ionization tandem mass spectrometry, and a robust and fast assay for the qualitative and quantitative analysis of theobromine in equine urine samples was validated. Urine specimens were extracted by means of solid-phase extraction cartridges, and concentrated extracts were analyzed by liquid chromatography interfaced to a triple-quadrupole mass spectrometer. In addition, the dissociation behavior of deuterated analogues to caffeine and theobromine allowed proposals for fragmentation routes of xanthine derivatives after atmospheric pressure ionization and collisionally activated dissociation. Copyright © 2004 John Wiley & Sons, Ltd. [source]

Pharmacotherapy Of The Ion Transport Defect In Cystic Fibrosis

CLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, Issue 11 2001
Karl Kunzelmann
SUMMARY 1. More than 1300 different mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) cause cystic fibrosis (CF), a disease characterized by deficient epithelial Cl, secretion and enhanced Na+ absorption. The clinical course of the disease is determined by the progressive lung disease. Thus, novel approaches in pharmacotherapy are based primarily on correction of the ion transport defect in the airways. 2. The current therapeutic strategies try to counteract the deficiency in Cl, secretion and the enhanced Na+ absorption. A number of compounds have been identified, such as genistein and xanthine derivatives, which directly activate mutant CFTR. Other compounds may activate alternative Ca2+ -activated Cl, channels or basolateral K+ channels, which supply the driving force for Cl, secretion. Apart from that, Na+ channel blockers, such as phenamil and benzamil, are being explored, which counteract the hyperabsorption of NaCl in CF airways. 3. Clinical trials are under way using purinergic compounds such as the P2Y2 receptor agonist INS365. Activation of P2Y2 receptors has been found to both activate Cl, secretion and inhibit Na+ absorption. 4. The ultimate goal is to recover Cl, channel activity of mutant CFTR by either enhancing synthesis and expression of the protein or by activating silent CFTR Cl, channels. Strategies combining these drugs with compounds facilitating Cl, secretion and inhibiting Na+ absorption in vivo may have the best chance to counteract the ion transport defect in cystic fibrosis. [source]