arsphenamine

The structure of Arsphenamine has been proposed to be akin to the azobenzene (A), but mass spectral studies published in 2005 suggest that it is actually a mixture of the trimer B and the pentamer C

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. Paul 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,^[1] because it was the 606th compound synthesized for testing.^[2] 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, Sahachiro Hata continued parallel investigation of the new medicine in Japan.^[3]

Structure

Since Salvarsan's discovery until recently it was believed that the structure featured an As=As bond. However, in 2005, an extensive mass spectral analysis showed that the actual structure is most likely to be a mixture of the cyclic trimer and a pentamer.^[1][4] The revised structure features As-As single bonds, not double bonds.

References