Suramin

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Suramin
QP51AE02 (WHO
)
Identifiers
  • 8,8'-{Carbonylbis[imino-3,1-phenylenecarbonylimino(4-methyl-3,1-phenylene)carbonylimino]}di(1,3,5-naphthalenetrisulfonic acid)
JSmol)
  • O=C(Nc1cc(ccc1C)C(=O)Nc3c2c(cc(cc2c(cc3)S(=O)(=O)O)S(=O)(=O)O)S(=O)(=O)O)c8cccc(NC(=O)Nc7cc(C(=O)Nc6cc(C(=O)Nc5c4c(cc(cc4c(cc5)S(=O)(=O)O)S(=O)(=O)O)S(=O)(=O)O)ccc6C)ccc7)c8
  • InChI=1S/C51H40N6O23S6/c1-25-9-11-29(49(60)54-37-13-15-41(83(69,70)71)35-21-33(81(63,64)65)23-43(45(35)37)85(75,76)77)19-39(25)56-47(58)27-5-3-7-31(17-27)52-51(62)53-32-8-4-6-28(18-32)48(59)57-40-20-30(12-10-26(40)2)50(61)55-38-14-16-42(84(72,73)74)36-22-34(82(66,67)68)24-44(46(36)38)86(78,79)80/h3-24H,1-2H3,(H,54,60)(H,55,61)(H,56,58)(H,57,59)(H2,52,53,62)(H,63,64,65)(H,66,67,68)(H,69,70,71)(H,72,73,74)(H,75,76,77)(H,78,79,80) checkY
  • Key:FIAFUQMPZJWCLV-UHFFFAOYSA-N checkY
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Suramin is a

injection into a vein.[4]

Suramin causes a fair number of side effects.

kidney problems, and low blood cell levels.[4] It is unclear if it is safe when breastfeeding.[2]

Suramin was made at least as early as 1916.

Centers for Disease Control (CDC).[3] In regions of the world where the disease is common suramin is provided for free by the World Health Organization (WHO).[7]

Medical uses

Suramin is used for treatment of human

Trypanosoma brucei gambiense, where pentamidine is recommended as first line.[9]

It has been used in the treatment of

river blindness (onchocerciasis).[2]

Pregnancy and breastfeeding

It is unknown whether it is safe for the baby when a woman takes it while breastfeeding.[2]

Adverse reactions

The most frequent adverse reactions are nausea, vomiting, diarrhea, abdominal pain, and a feeling of general discomfort. It is also common to experience various sensations in the skin, from crawling or tingling sensations, tenderness of palms and the soles, and numbness of hands, arm, legs or feet.[10] Other skin reactions include skin rash, swelling and stinging sensation.[10] Suramin can also cause loss of appetite and irritability.[10] Suramin causes non-harmful changes in urine during use, specifically making the urine cloudy.[10] It may exacerbate kidney disease.[11]

Less common side effects include extreme fatigue, ulcers in the mouth, and painful tender glands in the neck, armpits and groin.[10] Suramin uncommonly affects the eyes causing watery eyes, swelling around the eyes, photophobia, and changes or loss of vision.[10]

Rare side effects include hypersensitivity reactions causing difficulty breathing. Other rare systemic effects include decreased blood pressure, fever, rapid heart rate, and convulsions.[10] Other rare side effects include symptoms of liver dysfunction such as tenderness in upper abdomen, jaundice in eyes and skin, unusual bleeding or bruising.[10]

Suramin has been applied clinically to HIV/AIDS patients resulting in a significant number of fatal occurrences and as a result the application of this molecule was abandoned for this condition.[12]

Pharmacokinetics

Suramin is not orally bioavailable and must be given intravenously. Intramuscular and subcutaneous administration could result in local tissue inflammation or necrosis [citation needed]. Suramin is approximately 99-98% protein bound in the serum and has a half-life of 41–78 days average of 50 days; however, the pharmacokinetics of suramin can vary substantially between individual patients. Suramin does not distribute well into cerebral spinal fluid and its concentration in the tissues is equivalently lower than its concentration in the plasma. Suramin is not extensively metabolized and about 80% is eliminated via the kidneys.[11]

Chemistry

The molecular formula of suramin is C51H40N6O23S6. It is a

benzene rings, sandwiched by a pair of naphthalene moieties – plus four amide functional groups (in addition to the urea) and six sulfonic acid groups. When given as a medication, it is usually delivered as the sodium sulfonate salt as this formulation is water-soluble, though it does deteriorate rapidly in air.[11]

The

carboxyl (as acyl chloride) components. Various routes to these compounds have been developed, including starting from separate naphthalene structures and building towards an eventual unification by formation of the urea[13][14] or starting with a urea and appending successive groups.[15]

Mechanism of action

The mechanism of action for suramin is unclear, but it is thought that parasites are able to selectively uptake suramin via receptor-mediated endocytosis of drug that is bound to low-density lipoproteins and, to a lesser extent, other serum proteins.[11] Once inside parasites, suramin combines with proteins, especially trypanosomal glycolytic enzymes, to inhibit energy metabolism.[16]

History

Suramin was first made by the chemists Oskar Dressel, Richard Kothe and Bernhard Heymann at

brand name Germanin. The chemical structure of suramin was kept secret by Bayer for commercial and strategic reasons, but it was elucidated and published in 1924 by Ernest Fourneau and his team at the Pasteur Institute.[17]: 378–379 [18]

Research

It is also used as a research

D2 receptor,[19] the P2 receptor,[20][21] and ryanodine receptors.[22]

Suramin was studied as a possible treatment for prostate cancer in a clinical trial.[23]

Suramin has been studied in a mouse model of

autism and in a small phase I/II human trial.[24][25][26][27] Results from a randomized clinical study found no statistically significant effects of suramin (in either 10mg or 20mg doses) versus placebo on boys with moderate to severe autism spectrum disorder.[28]

Suramin is a reversible and competitive protein-tyrosine phosphatase (PTPases) inhibitor, also is the potent inhibitor of sirtuins, purified topoisomerase II and SARS-CoV-2 RNA-dependent RNA polymerase (RdRp).[29]

References

  1. ^ a b "Suramin Injection Advanced Patient Information". Drugs.com. 3 January 2020. Retrieved 11 January 2020.
  2. ^ a b c d e f "Micromedex Detailed Drug Information for the Consumer: Suramin (Injection route)". PubMed Health. 1 November 2016. Archived from the original on 8 September 2017.
  3. ^ a b "Our Formulary Infectious Diseases Laboratories CDC". www.cdc.gov. 22 September 2016. Archived from the original on 16 December 2016. Retrieved 30 November 2016.
  4. ^
    ISBN 9780471490791. Archived
    from the original on 30 November 2016.
  5. ISBN 9783540489948. Archived
    from the original on 30 November 2016.
  6. hdl:10665/325771
    . WHO/MVP/EMP/IAU/2019.06. License: CC BY-NC-SA 3.0 IGO.
  7. ^ "Trypanosomiasis, human African (sleeping sickness)". World Health Organization. February 2016. Archived from the original on 4 December 2016. Retrieved 7 December 2016.
  8. ^ "CDC Infectious Diseases Laboratory: Our Formulary". CDC. Archived from the original on 8 November 2016. Retrieved 8 November 2016.
  9. ^
    PMID 21628620
    .
  10. ^ a b c d e f g h "Suramin Injection Advanced Patient Information - Drugs.com". Archived from the original on 8 November 2016. Retrieved 8 November 2016.
  11. ^
    ISBN 9780071769396
    .
  12. PMID 3548350
    .
  13. PMID 15072843
    .
  14. PMID 16250663
    .
  15. doi:10.1016/j.tet.2009.03.033
    .
  16. ISBN 9780071802161
    .
  17. ISBN 9780471899792
    .
  18. ^ Fourneau E, Théfouël VJ, Vallée J (1924). "Sur une nouvelle série de médicaments trypanocides". Comptes Rendus des Séances de l'Académie des Sciences. 178: 675.
  19. PMID 8700151. Archived
    from the original on 8 September 2017.
  20. PMID 16968944
    .
  21. PMID 11171941. Archived
    from the original on 18 November 2016.
  22. PMID 16056233
    .
  23. S2CID 29107328
    .
  24. ^ LaFee S, Buschman H (26 May 2017). "Researchers Studying Century-Old Drug in Potential New Approach to Autism". UC San Diego Health. Archived from the original on 1 June 2017.
  25. PMID 24937094
    .
  26. PMID 28695149
    .
  27. ^ "Q and A - Suramin and Autism". UC Health - UC San Diego. Retrieved 27 July 2021.
  28. PMID 37932739
    .
  29. ^ "Suramin sodium salt". Selleck Chemicals.

Further reading

External links
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