Xanthine

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. Several stimulants are derived from xanthine, including caffeine, theophylline, and theobromine.

Xanthine

Names

Preferred IUPAC name

3,7-Dihydro-1H-purine-2,6-dione

Other names

1H-Purine-2,6-dione

Identifiers

CAS Number

69-89-6^Y

3D model (JSmol)

Interactive image

ChEBI

CHEBI:17712^N

ChEMBL

ChEMBL1424^Y

ChemSpider

1151^Y

DrugBank

DB02134^N

ECHA InfoCard

100.000.653

IUPHAR/BPS

4557

KEGG

C00385^N

PubChem CID

1188

UNII

1AVZ07U9S7^N

CompTox Dashboard (EPA)

DTXSID4035120

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

SMILES

c1[nH]c2c(n1)nc(nc2O)O

Properties

Chemical 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 (fire diamond)

2

1

0

Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).

verify (what is ^YN ?)

Infobox references

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.

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

Use and production

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

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. 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.

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. In high doses, they can lead to convulsions that are resistant to anticonvulsants. Methylxanthines induce gastric acid and pepsin secretions in the gastrointestinal tract. Methylxanthines are metabolized by cytochrome P450 in the liver.

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.

Pharmacology

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, and leukotriene and reduce inflammation and innate immunity. Adenosine receptor antagonists inhibit sleepiness-inducing adenosine.

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.

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.

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. 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.