Xanthine

Not to be confused with xanthene.

Xanthine
IUPAC name 3,7-Dihydropurine-2,6-dione
Other names 1H-Purine-2,6-diol
Identifiers
CAS number	69-89-6 Y= ?
PubChem	1188
ChemSpider	1151 Y
UNII	1AVZ07U9S7 N
DrugBank	DB02134
KEGG	C00385 N
ChEBI	CHEBI:17712 N
ChEMBL	CHEMBL1424 Y
Jmol-3D images	Image 1
SMILES c1[nH]c2c(n1)nc(nc2O)O
InChI InChI=1S/C5H4N4O2/c10-4-2-3(7-1-6-2)8-5(11)9-4/h1H,(H3,6,7,8,9,10,11) Y 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
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
N (verify) (what is: Y/N?) Except where noted otherwise, data are given for materials in their standard state (at 25 °C, 100 kPa)
Infobox references

Xanthine ( /ˈzænθiːn/ or /ˈzænθaɪn/; archaically xanthic acid) (3,7-dihydro-purine-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.^[1]

Xanthine is a product on the pathway of purine degradation.

• It is created from guanine by guanine deaminase.
• It is created from hypoxanthine by xanthine oxidoreductase.
• It is also created from xanthosine by purine nucleoside phosphorylase(PNP)^[2].

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.^[3][4] 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 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 treating the symptoms of asthma. In contrast to other, more potent stimulants, their main effect consists mainly of opposing the actions of the sleepiness-inducing adenosine, making them somewhat less effective as stimulants than sympathomimetic amines. 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.

Methylxanthines affect not only the airways but stimulate heart rate, force of contraction, cardiac arrhythmias at high concentrations. In the CNS they increase alertness, stimulate the respiratory centre, and are used for treatment of infantile apnea. 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. Methylated xanthines include caffeine, aminophylline, IBMX, paraxanthine, pentoxifylline,^[8] theobromine, and theophylline. These drugs act as both

1. competitive nonselective phosphodiesterase inhibitors ^[9] which raise intracellular cAMP, activate PKA, inhibit TNF-alpha ^[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	IUPAC nomenclature	Found In
Caffeine	CH3	CH3	CH3	1,3,7-trimethyl-1H-purine-2,6(3H,7H)-dione	Coffee, Guarana, Yerba mate, Tea, Kola
Theobromine	H	CH3	CH3	3,7-dihydro-3,7-dimethyl-1H-purine-2,6-dione	Chocolate, Yerba mate
Theophylline	CH3	CH3	H	1,3-dimethyl-7H-purine-2,6-dione	Tea, chocolate, Yerba mate
Xanthine	H	H	H	3,7-dihydro-purine-2,6-dione	plants, animals

See also

• Murchison meteorite
• Xanthene
• Xanthydrol
• Xanthone

References

1. ^ Spiller, Gene A. (1998). Caffeine. Boca Raton: CRC Press. ISBN 0-8493-2647-8. 
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, Zita; Botta, Oliver; Fogel, Marilyn L.; Sephton, Mark A.; Glavin, Daniel P.; Watson, Jonathan S.; Dworkin, Jason P.; Schwartz, Alan W. et al. (15 June 2008). "Extraterrestrial nucleobases in the Murchison meteorite". Earth and Planetary Science Letters 270 (1-2): 130–136. Bibcode 2008E&PSL.270..130M. doi:10.1016/j.epsl.2008.03.026. 
4. ^ AFP Staff (20 August 2009). "We may all be space aliens: study". AFP. http://afp.google.com/article/ALeqM5j_QHxWNRNdiW35Qr00L8CkwcXyvw. Retrieved 2011-08-14. 
5. ^ Callahan; Smith, K.E.; Cleaves, H.J.; Ruzica, J.; Stern, J.C.; Glavin, D.P.; House, C.H.; Dworkin, J.P. (11 August 2011). "Carbonaceous meteorites contain a wide range of extraterrestrial nucleobases". PNAS. doi:10.1073/pnas.1106493108. http://www.pnas.org/content/early/2011/08/10/1106493108. Retrieved 2011-08-15. 
6. ^ Steigerwald, John (08 August 2011). "NASA Researchers: DNA Building Blocks Can Be Made in Space". NASA. http://www.nasa.gov/topics/solarsystem/features/dna-meteorites.html. Retrieved 2011-08-10. 
7. ^ ScienceDaily Staff (09 August 2011). "DNA Building Blocks Can Be Made in Space, NASA Evidence Suggests". ScienceDaily. http://www.sciencedaily.com/releases/2011/08/110808220659.htm. Retrieved 2011-08-09. 
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 (Sao Paulo). 63 (3): 321–8. doi:10.1590/S1807-59322008000300006. PMC 2664230. PMID 18568240. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2664230. 
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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. PMID 9927365. http://ajrccm.atsjournals.org/cgi/pmidlookup?view=long&pmid=9927365. 
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. PMID 15634873. http://www.jimmunol.org/cgi/content/full/174/2/589. 
12. ^ 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. 
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'Oreal 
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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. doi:10.1021/jm00126a014. PMID 2724296. 
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21. ^ 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. http://linkinghub.elsevier.com/retrieve/pii/0006-2952(93)90168-V. 
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