Xanthine

Not to be confused with Xanthene or Xanthan.
Xanthine[1]
Names
Preferred IUPAC name
3,7-Dihydro-1H-purine-2,6-dione
Other names
1H-Purine-2,6-dione
Identifiers
3D model (JSmol)
ChEBI
ChEMBL
ChemSpider
DrugBank
ECHA InfoCard 100.000.653 Edit this at Wikidata
KEGG
UNII
  • InChI=1S/C5H4N4O2/c10-4-2-3(7-1-6-2)8-5(11)9-4/h1H,(H3,6,7,8,9,10,11) checkY
    Key: LRFVTYWOQMYALW-UHFFFAOYSA-N ☒N
  • InChI=1S/C5H4N4O2/c10-4-2-3(7-1-6-2)8-5(11)9-4/h1H,(H3,6,7,8,9,10,11)
  • InChI=1S/C5H4N4O2/c10-4-2-3(7-1-6-2)8-5(11)9-4/h1H,(H3,6,7,8,9,10,11)
    Key: LRFVTYWOQMYALW-UHFFFAOYSA-N
  • c1[nH]c2c(n1)nc(nc2O)O
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 (fire diamond)
NFPA 704 four-colored diamondHealth 2: Intense or continued but not chronic exposure could cause temporary incapacitation or possible residual injury. E.g. chloroformFlammability 1: Must be pre-heated before ignition can occur. Flash point over 93 °C (200 °F). E.g. canola oilInstability 0: Normally stable, even under fire exposure conditions, and is not reactive with water. E.g. liquid nitrogenSpecial hazards (white): no code
2
1
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 checkY☒N ?)

Xanthine (/ˈzænθiːn/ or /ˈzænθaɪn/, from Ancient Greek ξανθός xanthós 'yellow' for its yellowish-white appearance; archaically xanthic acid; systematic name 3,7-dihydropurine-2,6-dione) is a purine base found in most human body tissues and fluids, as well as in other organisms.[2] Several stimulants are derived from xanthine, including caffeine, theophylline, and theobromine.[3][4]

Xanthine is a product on the pathway of purine degradation.[2]

Xanthine is subsequently converted to uric acid by the action of the xanthine oxidase enzyme.[2]

Use and production

Xanthine is used as a drug precursor for human and animal medications, and is produced as a pesticide ingredient.[2]

Clinical significance

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 or influenza symptoms.[2] In contrast to other, more potent stimulants like sympathomimetic amines, xanthines mainly act to oppose the actions of adenosine, and increase alertness in the central nervous system.[2]

Toxicity

Methylxanthines (methylated xanthines), which include caffeine, aminophylline, IBMX, paraxanthine, pentoxifylline, theobromine, theophylline, and 7-methylxanthine (heteroxanthine), among others, affect the airways, increase heart rate and force of contraction, and at high concentrations can cause cardiac arrhythmias.[2] In high doses, they can lead to convulsions that are resistant to anticonvulsants.[2] Methylxanthines induce gastric acid and pepsin secretions in the gastrointestinal tract.[2] Methylxanthines are metabolized by cytochrome P450 in the liver.[2]

If swallowed, inhaled, or exposed to the eyes in high amounts, xanthines can be harmful, and they may cause an allergic reaction if applied topically.[2]

Pharmacology

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

In in vitro pharmacological studies, xanthines act as both competitive nonselective phosphodiesterase inhibitors and nonselective adenosine receptor antagonists. Phosphodiesterase inhibitors raise intracellular cAMP, activate PKA, inhibit TNF-α synthesis,[2][5][4] and leukotriene[6] and reduce inflammation and innate immunity.[6] Adenosine receptor antagonists [7] inhibit sleepiness-inducing adenosine.[2]

However, 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.[2][8][9][10][11][12]

Examples of xanthine derivatives
Name R1 R2 R3 R8 IUPAC nomenclature Found in
Xanthine H H H H 3,7-Dihydro-purine-2,6-dione Plants, animals
7-Methylxanthine H H CH3 H 7-methyl-3H-purine-2,6-dione Metabolite of caffeine and theobromine
Theobromine H CH3 CH3 H 3,7-Dihydro-3,7-dimethyl-1H-purine-2,6-dione Cacao (chocolate), yerba mate, kola, guayusa
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
Caffeine CH3 CH3 CH3 H 1,3,7-Trimethyl-1H-purine-2,6(3H,7H)-dione Coffee, guarana, yerba mate, tea, kola, guayusa, Cacao (chocolate)
8-Chlorotheophylline CH3 CH3 H Cl 8-Chloro-1,3-dimethyl-7H-purine-2,6-dione Synthetic pharmaceutical ingredient
8-Bromotheophylline CH3 CH3 H Br 8-Bromo-1,3-dimethyl-7H-purine-2,6-dione Pamabrom diuretic medication
Diprophylline CH3 CH3 C3H7O2 H 7-(2,3-Dihydroxypropyl)-1,3-dimethyl-3,7-dihydro-1H-purine-2,6-dione Synthetic pharmaceutical ingredient
IBMX CH3 C4H9 H H 1-Methyl-3-(2-methylpropyl)-7H-purine-2,6-dione
Uric acid H H H O 7,9-Dihydro-1H-purine-2,6,8(3H)-trione Byproduct of purine nucleotides metabolism and a normal component of urine

Pathology

People with rare genetic disorders, specifically xanthinuria and Lesch–Nyhan syndrome, lack sufficient xanthine oxidase and cannot convert xanthine to uric acid.[2]

Possible formation in absence of life

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, have been formed extraterrestrially.[13][14] 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.[15][16][17]

See also

References

  1. ^ Merck Index, 11th Edition, 9968.
  2. ^ a b c d e f g h i j k l m n o "Xanthine, CID 1188". PubChem, National Library of Medicine, US National Institutes of Health. 2019. Retrieved 28 September 2019.
  3. ^ Spiller, Gene A. (1998). Caffeine. Boca Raton: CRC Press. ISBN 0-8493-2647-8.
  4. ^ a b Katzung, Bertram G. (1995). Basic & Clinical Pharmacology. East Norwalk, Connecticut: Paramount Publishing. pp. 310, 311. ISBN 0-8385-0619-4.
  5. ^ 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.
  6. ^ 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. doi:10.4049/jimmunol.174.2.589. PMID 15634873.
  7. ^ 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.
  8. ^ 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.
  9. ^ 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.
  10. ^ 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.
  11. ^ 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. S2CID 23923058.
  12. ^ 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.
  13. ^ 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 (1–2): 130–136. arXiv:0806.2286. Bibcode:2008E&PSL.270..130M. doi:10.1016/j.epsl.2008.03.026. S2CID 14309508.
  14. ^ 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.
  15. ^ 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. Bibcode:2011PNAS..10813995C. doi:10.1073/pnas.1106493108. PMC 3161613. PMID 21836052.
  16. ^ Steigerwald, John (8 August 2011). "NASA Researchers: DNA Building Blocks Can Be Made in Space". NASA. Retrieved 2011-08-10.
  17. ^ ScienceDaily Staff (9 August 2011). "DNA Building Blocks Can Be Made in Space, NASA Evidence Suggests". ScienceDaily. Retrieved 2011-08-09.