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Cystamine

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Not to be confused with cysteamine.
Cystamine
Skeletal formula of cystamine
Ball-and-stick model of the cystamine molecule
Names
IUPAC name
2,2'-Dithiobis(ethylamine)
Other names
2,2'-Dithiobisethanamine
2-Aminoethyl disulfide
Decarboxycystine
Identifiers
3D model (JSmol)
Abbreviations AED
ChEBI
ChEMBL
ChemSpider
ECHA InfoCard 100.000.119 Edit this at Wikidata
UNII
  • InChI=1S/C4H12N2S2/c5-1-3-7-8-4-2-6/h1-6H2 checkY
    Key: APQPRKLAWCIJEK-UHFFFAOYSA-N checkY
  • InChI=1/C4H12N2S2/c5-1-3-7-8-4-2-6/h1-6H2
    Key: APQPRKLAWCIJEK-UHFFFAOYAQ
  • S(SCCN)CCN
Properties
C4H12N2S2
Molar mass 152.28 g/mol[1]
Appearance Viscous oil
Boiling point Decomposes
Miscible
Solubility in Ethanol Soluble[vague]
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 ?)

Cystamine (2,2'-dithiobisethanamine) is an organic disulfide. It is formed when cystine is heated, the result of decarboxylation. Cystamine is an unstable liquid and is generally handled as the dihydrochloride salt, C4H12N2S2·2HCl, which is stable to 203-214 °C at which point it decomposes. Cystamine is toxic if swallowed or inhaled and potentially harmful by contact.

Structure and synthesis

Cystamine is an organic disulfide which is formed when Cystine is heated as a result of decarboxylation. It is often used as sulfhydryl reagent, enzyme inhibitor and radiation-protective agent.[2] Thiols can be synthesized to disulfides like cystamine through chemical oxidation with various oxidizing agents (molecular oxygen, metal ion, metal oxide, DMSO, nitric oxide, halogen and sodium perborate), through electrochemical oxidation and through borohydride exchange resin (BER)-transition metal salts systems (like BER-CuSo4).[3]

Uses

Cystamine dihydrochloride is a useful reagent to derivatize various polymer monoliths for hydrophilic interaction liquid chromatography, as a crosslinking agent in the development of polymer hydrogels, and as a functional group in nanoparticles developed for siRNA and DNA delivery.

It has also been studied as a potential radioprotective agent.[4][5] Cystamine has also been studied as a potential medicinal compound in the case of Huntington's disease,[2] Alzheimer's disease[6] and carbon tetrachloride liver damage[7]

Interactions

Cystamine has been shown to interact with DNA and reversibly bind to it. Furthermore, cystamine is also able to bind to nucleoproteins. The nucleic acids that form from binding to DNA are more stable then unbound nucleic acids. Binding of cystamine to nucleoproteins makes them precipitate. The disulfides than binds to DNA and precipitate nucleoproteins have an analogous interaction like cadaverine and spermidine with DNA. The affinity of cystamine to DNA plays a role in the toxicity and radioprotecting properties of cystamine.[8]

Cystamine has also been shown to interact with the production of microtubule assemblies in bovine brain tissue. The interaction of cystamine interferes with the formation of microtubules, thus acting as an anti-microtubule at low concentrations. At high concentrations cystamine induces an abnormal tubulin polymerization. Five cystamine molecules can bind covalently to tubulin, this will cause mediated aggregation of tubulins.[9]

Toxicity

Multiple factors of potential cystamine toxicity have been described relating to hepatoxicity,[10] anti-coagulant activity[11] and skin sensitisation.[12] LD50/48H  values after intravenous administration have been described for rats (97 mg/kg of body weight) and mice (155.93 mg/kg of body weight).[4]

Cystamine inhibits coagulation factor XIa and thrombin, Therefore exhibiting anti-coagulant behavior. Furthermore, cystamine can cause liver damage by elevating cytosolic Ca2+ levels and subsequently activating a cytosolic proteolytic system. Skin sensitisation is a predicted effect of cystamine being a thiol.

Metabolism

Cystamine in the body is reduced into cysteamine and RS-cysteamine mixed disulfide by thiol-disulfide exchange. This is done by consumption of intracellular glutathione. Cysteamine is then oxidized to hypotaurine, this is done by the enzyme dioxygenase. The now formed hypotaurine is finally oxidized to taurine by hypotaurine dehydrogenase and the reduction of NAD+. Taurine is excreted out of the body or used in the body.[3]

References

  1. ^ Merck Index, 12th Edition, 2846.
  2. ^ a b "Cystamine – HOPES". web.stanford.edu. Retrieved 2017-03-17.
  3. ^ a b Sharma, Rashmi (1995). "The uptake and metabolism of cystamine and taurine by isolated perfused rat and rabbit lungs". The International Journal of Biochemistry & Cell Biology. 27 (7): 655–664. doi:10.1016/1357-2725(95)00038-Q.
  4. ^ a b Kuna, Pavel (2004). "Acute toxicity and radioprotective effects of amifostine (WR-2721) or cystamine in single whole body fission neutrons irradiated rats" (PDF). Journal of Applied Biomedicine. 2: 43–49.
  5. ^ Elks, J.; Ganellin, C. R. (1990). Dictionary of Drugs. doi:10.1007/978-1-4757-2085-3. ISBN 978-1-4757-2087-7.
  6. ^ Minarini, A.; Milelli, A.; Tumiatti, V.; Rosini, M.; Simoni, E.; Bolognesi, M. L.; Andrisano, V.; Bartolini, M.; Motori, E. (2012-02-01). "Cystamine-tacrine dimer: A new multi-target-directed ligand as potential therapeutic agent for Alzheimer's disease treatment". Neuropharmacology. Post-Traumatic Stress Disorder. 62 (2): 997–1003. doi:10.1016/j.neuropharm.2011.10.007. PMID 22032870.
  7. ^ de Toranzo, E.G.D.; Marzi, A.; Castro, J.A. (1981). "Effects of cysteine and cystamine on the carbon tetrachloride induced decrease in arachidonic acid content of rat liver microsomal phospholipids". Toxicology. 19 (1): 77–82. doi:10.1016/0300-483x(81)90067-6. PMID 7222059.
  8. ^ Petrov, Alexander I.; Dergachev, Ilya D.; Golovnev, Nicolay N. (2016-03-03). "Coordination model, stability constant, and kinetics study of cystamine and l-cystine with [PdCl4]2− in hydrochloric aqueous solutions". Journal of Coordination Chemistry. 69 (5): 748–762. doi:10.1080/00958972.2016.1139095.
  9. ^ Banerjee, Asok (1987). "The interaction of cystamine with bovine brain tubulin". European Journal of Biochemistry. 165 (2): 443–448. doi:10.1111/j.1432-1033.1987.tb11458.x.
  10. ^ Nicotera, Pierluigi (1996). "Cystamine induces toxicity in Hepatocytes through the elevation of cytosolic Ca2+ and the stimulation of nonlysosomal proteolytic system" (PDF). Journal of Biological Chemistry. 261: 14628–14635.
  11. ^ Aleman, Maria M.; Holle, Lori A.; Stember, Katherine G.; Devette, Christa I.; Monroe, Dougald M.; Wolberg, Alisa S. (2015-04-27). "Cystamine Preparations Exhibit Anticoagulant Activity". PLoS ONE. 10 (4): e0124448. doi:10.1371/journal.pone.0124448. ISSN 1932-6203. PMC 4411037. PMID 25915545.{{cite journal}}: CS1 maint: unflagged free DOI (link)
  12. ^ Langton, Kate; Patlewicz, Grace Y.; Long, Anthony; Marchant, Carol A.; Basketter, David A. (2006-12-01). "Structure–activity relationships for skin sensitization: recent improvements to Derek for Windows". Contact Dermatitis. 55 (6): 342–347. doi:10.1111/j.1600-0536.2006.00969.x.
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