Arsphenamine

Arsphenamine, also known as Salvarsan and 606, is a drug that was used to treat syphilis and trypanosomiasis. It was the first modern chemotherapeutic agent.

History

Sahachiro Hata discovered the anti-syphilitic activity of this compound in 1908 in the laboratory of Paul Ehrlich, during a survey of hundreds of newly synthesized organic arsenical compounds. Ehrlich had theorized that by screening many compounds a drug could be discovered with anti-microbial activity. Ehrlich's team began their search for such a "magic bullet" among chemical derivatives of the dangerously toxic drug atoxyl. This was the first organized team effort to optimize the biological activity of a lead compound through systematic chemical modifications, the basis for nearly all modern pharmaceutical research.

Arsphenamine was marketed under the trade name "Salvarsan" in 1910. It was also called "606",cite web |url=http://pubs.acs.org/cen/coverstory/83/8325/8325salvarsan.html |title=Chemical & Engineering News: Top Pharmaceuticals: Salvarsan |accessdate=2007-08-25 |format= |work=] because it was the 606th compound synthesized for testing [In Germany it was the practice to designate compounds by their development number. Another compound known commonly in Germany by its number is Parathion, which was the 605th compound to be developed in search for insecticide. It is commonly known as E605 (E stands for Entwicklungsnummer (German for "development number")] . Salvarsan was the first organic anti-syphillitic, and a great improvement over the inorganic mercury compounds that had been used previously. A more soluble (but slightly less effective) arsenical compound, Neosalvarsan, ("neoarsphenamine"), became available in 1912. These arsenical compounds came with considerable risk of side effects, and they were supplanted as treatments for syphilis in the 1940s by penicillin.

The bacterium that causes syphilis is a spirochete, "Treponema pallidum". Arsphenamine is not toxic to spirochetes until it has been converted to an active form by the body.

After leaving Erlich's laboratory, Hata continued parallel investigation of the new medicine in Japan. [Izumi, Yoshio; and Isozumi, Kazuo. (2001). [http://www.kjm.keio.ac.jp/past/50/2/91.pdf Modern Japanese medical history and the European influence.] "Keio Journal of Medicine" 50 (2), 91-99. PMID 11450598.]

tructure

The structure was believed to feature an As=As bond. However, in 2005, it was shown to be a mixture of the cyclic trimer and a pentamer. [cite web |url=http://www1.accsnet.ne.jp/~kentaro/yuuki/mow/0501/salvarsan.html |title=accsnet.ne.jp |accessdate=2007-08-25 |format= |work=] cite journal |author=Lloyd NC, Morgan HW, Nicholson BK, Ronimus RS |title=The composition of Ehrlich's salvarsan: resolution of a century-old debate |journal=Angew. Chem. Int. Ed. Engl. |volume=44 |issue=6 |pages=941–4 |year=2005 |pmid=15624113 |doi=10.1002/anie.200461471] ] The revised structure features As-As single bonds, not double bonds.

In History

Vladimir Lenin was treated by salvarsan before his death which supports the hypothesis that he died from syphilis [ [http://discovermagazine.com/2005/jan/syphilis-killed-lenin 96: Report: Syphilis Killed Lenin | Infectious Diseases | DISCOVER Magazine ] ] .

ee also

*"Dr. Ehrlich's Magic Bullet" a 1940 movie released by Warner Brothers starring Edward G. Robinson as Ehrlich.
*"Out of Africa," 1937 novel and basis for a 1985 movie.

References