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Arsenicals

Arsenicals and other metallic compounds have been used in medicine at least since the time of the sixteenth century Swiss physician and alchemist, Paracelsus (Philippus Theophrastus Bombastus von Hohenheim). The explorer David Livingstone was among those who used arsenic in the treatment of nagana, a disease of ungulates, later shown by David Bruce (of Brucella fame) to be caused by trypanosomes. Ehrlich had also exhibited a passing interest in these compounds, and this was rekindled in 1905 by a report from the Liverpool School of Tropical Medicine that one arsenical, atoxyl, protected mice from trypanosomal infection. Ehrlich resumed research into arsenical compounds and visited the Liverpool School in 1907.
Despite its name, atoxyl was anything but atoxic and Ehrlich, together with his chemist Alfred Bertheim, set about trying to produce safer arsenical derivatives. A Japanese assistant, Sahachiro Hata, joined the team in 1909 and they studied the new compounds on spirochaetes, which were thought to exhibit similarities to trypanosomes. Later that year Hata showed that an arsenical compound  cured rabbits infected with the spirochaetes of syphilis and displayed an acceptable safety profile. The compound was named arsphenamine and marketed as Salvarsan, constituting the first really efficacious antibacterial agent. An improved derivative, neoarsphenamine (Neosalvarsan), was produced in Ehrlich's laboratory in 1912. Later, other compounds useful for the treatment of African sleeping sickness, and tryparsamide where identified, including melarsoprol (Mel B).

 

 

Nagana                                                Atoxyl        Salvarsan                            Melasroprol

 

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