Xanthine

Xanthine[1]
Names
IUPAC name
3,7-Dihydropurine-2,6-dione
Other names
1H-Purine-2,6-dione
Identifiers
69-89-6 YesY
3D model (Jmol) Interactive image
ChEBI CHEBI:17712 N
ChEMBL ChEMBL1424 YesY
ChemSpider 1151 YesY
DrugBank DB02134 N
ECHA InfoCard 100.000.653
4557
KEGG C00385 N
PubChem 1188
UNII 1AVZ07U9S7 N
Properties
C5H4N4O2
Molar mass 152.11 g/mol
Appearance White solid
Melting point decomposes
1 g/ 14.5 L @ 16 °C
1 g/1.4 L @ 100 °C
Hazards
NFPA 704
Flammability code 1: Must be pre-heated before ignition can occur. Flash point over 93 °C (200 °F). E.g., canola oil Health code 2: Intense or continued but not chronic exposure could cause temporary incapacitation or possible residual injury. E.g., chloroform Reactivity code 0: Normally stable, even under fire exposure conditions, and is not reactive with water. E.g., liquid nitrogen Special hazards (white): no codeNFPA 704 four-colored diamond
1
2
0
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
N verify (what is YesYN ?)
Infobox references

Xanthine (/ˈzænθiːn/ or /ˈzænθaɪn/; archaically xanthic acid) (3,7-dihydropurine-2,6-dione), is a purine base found in most human body tissues and fluids and in other organisms. A number of stimulants are derived from xanthine, including caffeine and theobromine.[2]

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 isotopic ratios of organic compounds found in the Murchison meteorite, suggested that xanthine and related chemicals, including the RNA component uracil, were formed extraterrestrially.[4][5] In August 2011, a report, based on NASA studies with meteorites found on Earth, was published suggesting xanthine and related organic molecules, including the DNA and RNA components adenine and guanine, were found in outer space.[6][7][8]

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,[9] theobromine, and theophylline, affect not only the airways but stimulate heart rate, force of contraction, and 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 [10] which raise intracellular cAMP, activate PKA, inhibit TNF-α [9][11] and leukotriene [12] synthesis, and reduce inflammation and innate immunity [12] and
  2. nonselective adenosine receptor antagonists [13] 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.[14][15][16][17][18][19][20][21][22][23][24][25][26] 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
NameR1R2R3R8IUPAC nomenclatureFound In
XanthineHHHH3,7-dihydro-purine-2,6-dionePlants, animals
CaffeineCH3CH3CH3H1,3,7-trimethyl-1H-purine-2,6(3H,7H)-dioneCoffee, Guarana, Yerba mate, Tea, Kola, Guayusa, Holly
TheobromineHCH3CH3H3,7-dihydro-3,7-dimethyl-1H-purine-2,6-dioneCacao (chocolate), Yerba mate, Kola, Guayusa, Holly
TheophyllineCH3CH3HH1,3-dimethyl-7H-purine-2,6-dioneTea, Cacao (chocolate), Yerba mate, Kola
ParaxanthineCH3HCH3H1,7-dimethyl-7H-purine-2,6-dioneAnimals that have consumed caffeine
8-ChlorotheophyllineCH3CH3HClDimenhydrinate

Detection

See also

References

  1. ↑ Merck Index, 11th Edition, 9968.
  2. ↑ Spiller, Gene A. (1998). Caffeine. Boca Raton: CRC Press. ISBN 0-8493-2647-8.
  3. ↑ 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.
  4. ↑ 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. arXiv:0806.2286Freely accessible. Bibcode:2008E&PSL.270..130M. doi:10.1016/j.epsl.2008.03.026.
  5. ↑ AFP Staff (13 June 2008). "We may all be space aliens: study". AFP. Archived from the original on June 17, 2008. Retrieved 2011-08-14.
  6. ↑ 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. doi:10.1073/pnas.1106493108. PMC 3161613Freely accessible. PMID 21836052.
  7. ↑ Steigerwald, John (8 August 2011). "NASA Researchers: DNA Building Blocks Can Be Made in Space". NASA. Retrieved 2011-08-10.
  8. ↑ ScienceDaily Staff (9 August 2011). "DNA Building Blocks Can Be Made in Space, NASA Evidence Suggests". ScienceDaily. Retrieved 2011-08-09.
  9. 1 2 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. doi:10.1590/S1807-59322008000300006. PMC 2664230Freely accessible. PMID 18568240.
  10. ↑ Essayan DM. (2001). "Cyclic nucleotide phosphodiesterases". J Allergy Clin Immunol. 108 (5): 671–80. doi:10.1067/mai.2001.119555. PMID 11692087.
  11. ↑ 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. doi:10.1164/ajrccm.159.2.9804085. PMID 9927365.
  12. 1 2 Peters-Golden M, Canetti C, Mancuso P, Coffey MJ (2005). "Leukotrienes: underappreciated mediators of innate immune responses". J Immunol. 174 (2): 589–94. doi:10.4049/jimmunol.174.2.589. PMID 15634873.
  13. ↑ Daly JW, Jacobson KA, Ukena D (1987). "Adenosine receptors: development of selective agonists and antagonists". Prog Clin Biol Res. 230 (1): 41–63. PMID 3588607.
  14. ↑ MacCorquodale DW. THE SYNTHESIS OF SOME ALKYLXANTHINES. Journal of the American Chemical Society. 1929 July;51(7):2245–2251. doi:10.1021/ja01382a042
  15. ↑ 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.
  16. ↑ Constantin Koulbanis, Claude Bouillon, Patrick Darmenton,"Cosmetic compositions having a slimming action", US patent 4288433, granted 1981-09-04 , assigned to L'Oréal
  17. ↑ 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. doi:10.1021/jm00157a035. PMID 3806581.
  18. ↑ Daly JW, Jacobson KA, Ukena D (1987). "Adenosine receptors: development of selective agonists and antagonists". Progress in Clinical and Biological Research. 230: 41–63. PMID 3588607.
  19. ↑ 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. doi:10.1016/0024-3205(88)90517-6. PMID 2456442.
  20. ↑ 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. doi:10.1021/jm00126a014. PMID 2724296.
  21. ↑ Daly JW, Hide I, Müller CE, Shamim M (1991). "Caffeine analogs: structure-activity relationships at adenosine receptors". Pharmacology. 42 (6): 309–21. doi:10.1159/000138813. PMID 1658821.
  22. ↑ Ukena D, Schudt C, Sybrecht GW (February 1993). "Adenosine receptor-blocking xanthines as inhibitors of phosphodiesterase isozymes". Biochemical Pharmacology. 45 (4): 847–51. doi:10.1016/0006-2952(93)90168-V. PMID 7680859.
  23. ↑ Daly JW (July 2000). "Alkylxanthines as research tools". Journal of the Autonomic Nervous System. 81 (1–3): 44–52. doi:10.1016/S0165-1838(00)00110-7. PMID 10869699.
  24. ↑ Daly JW (August 2007). "Caffeine analogs: biomedical impact". Cellular and Molecular Life Sciences : CMLS. 64 (16): 2153–69. doi:10.1007/s00018-007-7051-9. PMID 17514358.
  25. ↑ 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. doi:10.1002/med.20108. PMID 17668454.
  26. ↑ 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. doi:10.1021/cr0682195. PMID 18181659.

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