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Xanthine

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Xanthine

Xanthine
Identifiers
CAS number  YesY= ?
PubChem
ChemSpider  YesY
UNII  N
DrugBank
KEGG  N
ChEBI  N
ChEMBL  YesY
Jmol-3D images Image 1
Properties
Molecular formula C5H4N4O2
Molar mass 152.11 g/mol
Appearance White solid
Melting point decomposes
Solubility in water 1 g/ 14.5 L @ 16 °C
1 g/1.4 L @ 100 °C
Hazards
NFPA 704
1
2
0
Except where noted otherwise, data are given for materials in their standard state (at 25 °C (77 °F), 100 kPa)
 N   YesY/N?)

Xanthine ( or ; archaically xanthic acid) (3,7-dihydro-purine-2,6-dione), is a stimulants are derived from xanthine, including caffeine and theobromine.[1]

Xanthine is a product on the pathway of purine degradation.

Xanthine is subsequently converted to uric acid by the action of the xanthine oxidase enzyme.

Studies reported in 2008, based on 12C/13C DNA and RNA components adenine and guanine, were made in outer space.[5][6][7]

Pathology

People with the rare genetic disorder xanthinuria lack sufficient xanthine oxidase and cannot convert xanthine to uric acid.

Clinical significance of xanthine derivatives

Derivatives of xanthine (known collectively as xanthines) are a group of alkaloids commonly used for their effects as mild stimulants and as bronchodilators, notably in the treatment of asthma symptoms. In contrast to other, more potent stimulants like sympathomimetic amines, xanthines mainly act to oppose the actions of the sleepiness-inducing adenosine, and increase alertness in the central nervous system. They also stimulate the respiratory centre, and are used for treatment of infantile apnea. Due to widespread effects, the therapeutic range of xanthines is narrow, making them merely a second-line asthma treatment. The therapeutic level is 10-20 micrograms/mL blood; signs of toxicity include tremor, nausea, nervousness, and tachycardia/arrhythmia.

Methylated xanthines (methylxanthines), which include caffeine, aminophylline, IBMX, paraxanthine, pentoxifylline,[8] theobromine, and theophylline, affect not only the airways but stimulate heart rate, force of contraction, cardiac arrhythmias at high concentrations. In high doses they can lead to convulsions that are resistant to anticonvulsants. Methylxanthines induce acid and pepsin secretions in the GI tract. Methylxanthines are metabolized by cytochrome P450 in the liver.

These drugs act as both:

  1. competitive nonselective phosphodiesterase inhibitors [9] which raise intracellular cAMP, activate PKA, inhibit TNF-α [8][10] and leukotriene [11] synthesis, and reduce inflammation and innate immunity [11] and
  2. nonselective adenosine receptor antagonists [12] which inhibit sleepiness-inducing adenosine.

But different analogues show varying potency at the numerous subtypes, and a wide range of synthetic xanthines (some nonmethylated) have been developed searching for compounds with greater selectivity for phosphodiesterase enzyme or adenosine receptor subtypes.[13][14][15][16][17][18][19][20][21][22][23][24][25] Xanthines are also found very rarely as constituents of nucleic acids.

Caffeine: R1 = R2 = R3 = CH3
Theobromine: R1 = H, R2 = R3 = CH3
Theophylline: R1 = R2 = CH3, R3 = H

Selected Xanthines
Name R1 R2 R3 R8 IUPAC nomenclature Found In
Xanthine H H H H 3,7-dihydro-purine-2,6-dione Plants, animals
Caffeine CH3 CH3 CH3 H 1,3,7-trimethyl-1H-purine-2,6(3H,7H)-dione Coffee, Guarana, Yerba mate, Tea, Kola, Guayusa, Yaupon holly
Theobromine H CH3 CH3 H 3,7-dihydro-3,7-dimethyl-1H-purine-2,6-dione Cacao (chocolate), Yerba mate, Kola, Guayusa, Yaupon holly
Theophylline CH3 CH3 H H 1,3-dimethyl-7H-purine-2,6-dione Tea, Cacao (chocolate), Yerba mate, Kola
Paraxanthine CH3 H CH3 H 1,7-dimethyl-7H-purine-2,6-dione Animals that have consumed caffeine
8-Chlorotheophylline CH3 CH3 H Cl Dimenhydrinate


See also

References

  1. ^ Spiller, Gene A. (1998). Caffeine. Boca Raton: CRC Press.  
  2. ^ Voet, Donald; Voet, Judith; Pratt, Charlotte (2008). "The Major Pathways of Purine Catabolism in Animals", Fundamentals of Biochemistry: Life at the Molecular Level, p. 840.
  3. ^ Martins, Z.; Botta, O.; Fogel, M. L.; Sephton, M. A.; Glavin, D. P.; Watson, J. S.; Dworkin, J. P.; Schwartz, A. W.; Ehrenfreund, P. (2008). "Extraterrestrial nucleobases in the Murchison meteorite". Earth and Planetary Science Letters 270: 130–136.  
  4. ^  
  5. ^ Callahan, M. P.; Smith, K. E.; Cleaves, H. J.; Ruzicka, J.; Stern, J. C.; Glavin, D. P.; House, C. H.; Dworkin, J. P. (2011). "Carbonaceous meteorites contain a wide range of extraterrestrial nucleobases". Proceedings of the National Academy of Sciences 108 (34): 13995–8.  
  6. ^ Steigerwald, John (8 August 2011). "NASA Researchers: DNA Building Blocks Can Be Made in Space".  
  7. ^ ScienceDaily Staff (9 August 2011). "DNA Building Blocks Can Be Made in Space, NASA Evidence Suggests".  
  8. ^ a b Deree J, Martins JO, Melbostad H, Loomis WH, Coimbra R. (2008). "Insights into the regulation of TNF-alpha production in human mononuclear cells: the effects of non-specific phosphodiesterase inhibition". Clinics (São Paulo). 63 (3): 321–8.  
  9. ^ Essayan DM. (2001). "Cyclic nucleotide phosphodiesterases". J Allergy Clin Immunol. 108 (5): 671–80.  
  10. ^ Marques LJ, Zheng L, Poulakis N, Guzman J, Costabel U (February 1999). "Pentoxifylline inhibits TNF-alpha production from human alveolar macrophages". Am. J. Respir. Crit. Care Med. 159 (2): 508–11.  
  11. ^ a b Peters-Golden M, Canetti C, Mancuso P, Coffey MJ. (2005). "Leukotrienes: underappreciated mediators of innate immune responses". J Immunol. 174 (2): 589–94.  
  12. ^ Daly JW, Jacobson KA, Ukena D. (1987). "Adenosine receptors: development of selective agonists and antagonists". Prog Clin Biol Res. 230 (1): 41–63.  
  13. ^ MacCorquodale DW. THE SYNTHESIS OF SOME ALKYLXANTHINES. Journal of the American Chemical Society. 1929 July;51(7):2245–2251. doi:10.1021/ja01382a042
  14. ^ WO patent 1985002540, Sunshine A, Laska EM, Siegel CE, "ANALGESIC AND ANTI-INFLAMMATORY COMPOSITIONS COMPRISING XANTHINES AND METHODS OF USING SAME", granted 1989-03-22, assigned to RICHARDSON-VICKS, INC.
  15. ^ Constantin Koulbanis, Claude Bouillon, Patrick Darmenton,"Cosmetic compositions having a slimming action", US patent 4288433, granted 1981-09-04 , assigned to L'Oréal 
  16. ^ Daly JW, Padgett WL, Shamim MT (July 1986). "Analogues of caffeine and theophylline: effect of structural alterations on affinity at adenosine receptors". Journal of Medicinal Chemistry 29 (7): 1305–8.  
  17. ^ Daly JW, Jacobson KA, Ukena D (1987). "Adenosine receptors: development of selective agonists and antagonists". Progress in Clinical and Biological Research 230: 41–63.  
  18. ^ Choi OH, Shamim MT, Padgett WL, Daly JW (1988). "Caffeine and theophylline analogues: correlation of behavioral effects with activity as adenosine receptor antagonists and as phosphodiesterase inhibitors". Life Sciences 43 (5): 387–98.  
  19. ^ Shamim MT, Ukena D, Padgett WL, Daly JW (June 1989). "Effects of 8-phenyl and 8-cycloalkyl substituents on the activity of mono-, di-, and trisubstituted alkylxanthines with substitution at the 1-, 3-, and 7-positions". Journal of Medicinal Chemistry 32 (6): 1231–7.  
  20. ^ Daly JW, Hide I, Müller CE, Shamim M (1991). "Caffeine analogs: structure-activity relationships at adenosine receptors". Pharmacology 42 (6): 309–21.  
  21. ^ Ukena D, Schudt C, Sybrecht GW (February 1993). "Adenosine receptor-blocking xanthines as inhibitors of phosphodiesterase isozymes".  
  22. ^ Daly JW (July 2000). "Alkylxanthines as research tools". Journal of the Autonomic Nervous System 81 (1–3): 44–52.  
  23. ^ Daly JW (August 2007). "Caffeine analogs: biomedical impact". Cellular and Molecular Life Sciences : CMLS 64 (16): 2153–69.  
  24. ^ González MP, Terán C, Teijeira M (May 2008). "Search for new antagonist ligands for adenosine receptors from QSAR point of view. How close are we?". Medicinal Research Reviews 28 (3): 329–71.  
  25. ^ Baraldi PG, Tabrizi MA, Gessi S, Borea PA (January 2008). "Adenosine receptor antagonists: translating medicinal chemistry and pharmacology into clinical utility". Chemical Reviews 108 (1): 238–63.  
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