Suramin

This article provides information on the chemical suramin, also known under the German trade name Germanin . For other meanings of Germanin , see Germanin (disambiguation) .

Structural formula
General
Non-proprietary name	Suramin
other names	8 - ((4-Methyl-3 - ((3 - ((3 - ((2-methyl-5 - ((4,6,8-trisulfonaphthalen-1-yl) carbamoyl) phenyl) carbamoyl) phenyl) carbamoylamino) benzoyl) amino) benzoyl) amino) naphthalene-1,3,5-trisulfonic acid ( IUPAC )
Molecular formula	C 51 H 40 N 6 O 23 S 6 (suramin) C 51 H 34 N 6 Na 6 O 23 S 6 (suramin hexasodium salt)
Brief description	White to pale yellow or pink powder
External identifiers / databases
CAS number 145-63-1 (Suramin) 129-46-4 (suramin hexasodium salt) EC number 205-658-4 ECHA InfoCard 100.005.145 PubChem 5361 ChemSpider 5168 DrugBank DB04786 Wikidata Q425946
Drug information
ATC code	P01 CX02
Drug class	Antiprotozoic
properties
Molar mass	1297.29 g · mol -1 (suramin) 1429.17 g · mol -1 (hexasodium salt)
solubility	easily soluble in water (hexasodium salt) little in ethanol (hexasodium salt) insoluble in benzene , diethyl ether , chloroform (hexasodium salt)
safety instructions
Please note the exemption from the labeling requirement for drugs, medical devices, cosmetics, food and animal feed GHS hazard labeling no classification available
Toxicological data	620 mg kg −1 ( LD 50 ,  mouse ,  iv )
As far as possible and customary, SI units are used. Unless otherwise noted, the data given apply to standard conditions .

Suramin is a colorless analogue of the azo dye trypan blue . Suramin (best known trade name: Germanin ) has been used as an antiprotozoal against sleeping sickness and other trypanosomal diseases since the 1920s .

history

Collage picture from 1938 on the topic of "Combating sleeping sickness by German colonial doctors" . Above Robert Koch , who laid the foundations for the research project as a microbiologist , next to sleeping wards and treatment in Cameroon, below the drug Suramin or "Bayer 205"

Suramin was first synthesized in 1916 by chemists Oskar Dressel , Richard Kothe and Bernhard Heymann from Bayer & Co. in Elberfeld under the internal name Bayer 205 (all three received the Adolf von Baeyer medal for this ). The medical development and the accompanying animal experiments took place in the chemotherapeutic laboratory in Elberfeld under the direction of Wilhelm Roehl . In Germany, the active ingredient was marketed under the trade name Germanin . The formula was kept secret for economic reasons, but was deciphered and published in 1924 by Ernest Fourneau of the Pasteur Institute .

Use as an anti-parasitic agent

The active ingredient suramin is extremely toxic to cells. Its use carries the risk of significant side effects, but it kills the parasites when dosed appropriately. At the beginning of the 1920s, medicine thus had for the first time an effective remedy against sleeping sickness , which until then had been rampant in large parts of Africa with devastating epidemics . The tests in East Africa were carried out by the Robert Koch student Friedrich Karl Kleine . Since then, suramin has also proven itself in other trypanosomal diseases. It has also been used successfully to combat onchocerciasis , a common tropical worm disease that causes river blindness .

Testing new applications

For some time, suramin has been clinically tested as a therapeutic agent against the HI virus and various cancers , lymphomas , lung , kidney and prostate cancers . Its inhibitory effect on heparanase is known in this context and is a possible mechanism.

A new discovery is that suramin can significantly inhibit programmed cell death ( apoptosis ) in liver cells , although it promotes this in other tissues. Acute liver failure can occur with hepatitis B infections and drug or fungal poisoning, a fatal process for which there is as yet no drug therapy.

At the University of California (San Diego), Suramin was able to successfully treat symptoms similar to autism in mouse experiments. The experiment is based on the assumption that a type of “non-genetic autism ” is caused by a faulty cell interaction. However, the existence of “non-genetic autism” has not been proven, which is why such experiments usually do not speak of autism, but only of symptoms similar to autism.

A clinical study with the low-dose active ingredient (20 mg / kg), in which 10 children and adolescents aged 5–14 years took part, led to improvements in the categories of language, social interaction and stereotypical behavior.

Testing against AIDS

The team of Robert Gallo had shown that suramin by inhibiting reverse transcriptase reduced the spread of the HIV virus in live animals. Therefore, at the end of the 1980s, suramin was tested as an agent against HIV / AIDS , which resulted in several serious side effects. In one study, 16 of 98 patients died during treatment or shortly afterwards. Another study, which also had severe side effects, showed no effect on the development of opportunistic infections during therapy and thus no clinical benefit in HIV-related diseases.

Trade names

Antrypol, Bayer 205, Belganyl, Fourneau 309, Germanin, Moranyl, Naganol, Naginin, Naphuride.

Individual evidence

1. ↑ ^{a b c d e} entry on Suramin. In: Römpp Online . Georg Thieme Verlag, accessed on March 10, 2011.
2. ↑ This substance has either not yet been classified with regard to its hazardousness or a reliable and citable source has not yet been found.
3. ↑ Walter Sneader: Drug Discovery: A History. John Wiley & Sons, 2005, ISBN 0-471-89979-8 , pp. 378f.
4. ^ Ernest Fourneau: Sur une nouvelle série de médicaments trypanocides. In: CR Séances Acad. Sci. No. 178, 1924, p. 675.
5. ↑ A. Meirovitz, R. Goldberg, A. Binder, AM Rubinstein, E. Hermano, M. Elkin: Heparanase in inflammation and inflammation-associated cancer. In: The FEBS journal. Volume 280, Number 10, May 2013, pp. 2307-2319, ISSN  1742-4658 . doi : 10.1111 / febs.12184 . PMID 23398975 . PMC 3651782 (free full text).
6. ↑ Suramin in acute liver failure ( Memento of the original from May 19, 2004 in the Internet Archive ) Info: The archive link was inserted automatically and has not yet been checked. Please check the original and archive link according to the instructions and then remove this notice. . 
7. ↑ Single dose reverses autism-like symptoms in mice. Retrieved June 19, 2014.
8. ↑ Helen Briggs: Autism 'begins long before birth'. In: bbc.com. March 27, 2014, accessed May 29, 2017 . 
9. ↑ R. Stoner, ML Chow et al: Patches of disorganization in the neocortex of children with autism. In: The New England Journal of Medicine . Volume 370, Number 13, March 2014, pp. 1209-1219, doi: 10.1056 / NEJMoa1307491 . PMID 24670167 , PMC 4499461 (free full text).
10. ^ S. De Rubeis, JD Buxbaum: Genetics and genomics of autism spectrum disorder: Embracing complexity. In: Human Molecular Genetics . [electronic publication before printing] July 2015, doi: 10.1093 / hmg / ddv273 . PMID 26188008 (Review).
11. ↑ RK Naviaux, B. Curtis, K. Li, JC Naviaux, AT Bright, GE Reiner, M. Westerfield, S. Goh, WA Alaynick, L. Wang, EV Capparelli, C. Adams, J. Sun, S. Jain , F. He, DA Arellano, LE Mash, L. Chukoskie, A. Lincoln, J. Townsend: Low-dose suramin in autism spectrum disorder: a small, phase I / II, randomized clinical trial. In: Annals of Clinical and Translational Neurology. 2017, pp. 2328–9503. doi: 10.1002 / acn3.424 .
12. ↑ Luc Montagnier, Robert Gallo: AZT - the first drug therapy for HIV . Animal research
13. ↑ BD Cheson, AM Levine, D. Mildvan, LD Kaplan, P. Wolfe, A. Rios, JE Groopman, P. Gill, PA Volberding, BJ Poiesz include: suramin therapy in AIDS and related disorders. Report of the US Suramin Working Group . PMID 3650339
14. ↑ Lawrence D. Kaplan, Peter R. Wolfe, Paul A. Volberding, Paul Feorino, Donald I. Abrams, Jay A. Levy, Roberta Wong, Lilian Kaufman, Michael S. Gottlieb: Lack of response to suramin in patients with AIDS and AIDS-related complex. In: The American Journal of Medicine. 82 (3), 1987, pp. 615-620. PMID 3548350

literature

• YL Zhang et al .: Suramin is an active site-directed, reversible, and tight-binding inhibitor of protein-tyrosine phosphatases. In: J. Biol. Chem. Volume 273, 1998, pp. 12281-12287. PMID 9575179 PDF .
• Eva Anne Jacobi: The Germanic sleeping sickness drug as a propaganda instrument: Reception in literature and film at the time of National Socialism. In: Würzburg medical history reports. Volume 29, 2010, pp. 43-72.

Web links

• Suramin. ( Memento of June 9, 2007 in the Internet Archive ) In: Encyclopedia of Cancer. (engl.)

This article is about a health issue. It is not used for self-diagnosis and does not replace a diagnosis by a doctor. Please note the information on health issues !