Syphilis treatment organoarsenicals

Arsenic compounds have been used in medicine since the time of Hippocrates, ca. 400 BCE (Woolson 1975). Inorganic arsenicals have been used for centuries, and organoarsenicals for at least a century in the treatment of syphilis, yaws, amoebic dysentery, and trypanosomiasis (NAS... 

The use of coordination compounds, or metal-based drugs, to treat disease. Examples are the historical use of organoarsenicals in the treatment of syphilis, the more recent use of m-dichlorodiammineplatinum(II) in the treatment of certain types of cancer, and the use for 50 years of complexes of gold in the treatment of rheumatoid arthritis. 

Although now essentially obsolete for the treatment of human diseases because of their toxicities, organoarsenic compounds were the first synthetic organic pharmaceutical agents and were widely used in the early 1900s. The first pharmaceutical application was that of atoxyl (the sodium salt of 4-aminophenylarsinic acid), which was used to treat sleeping sickness. The synthesis of Salvarsan by Dr. Paul Ehrlich in 1907 was a development that may be considered the beginning of modem chemotherapy (chemical treatment of disease). Salvarsan was widely used for the treatment of syphilis. Toxic effects of Salvarsan included jaundice and encephalitis (brain inflammation). 

The first significant organoarsenical dmg was synthesized by Pierre Antoine Bechamp (1816-1908) by chemically reacting arsenic acid with aniline [16,17]. Bechamp isolated a colorless compound that he regarded as an anilide of arsenic acid (Fig. 2a). Some 40 years after its initial synthesis, Wolferstan Thomas in Liverpool demonstrated the trypanocidal activity of atoxyl [18] and a few years later it was also used in the treatment of syphilis [19]. Hence, Bechamp s anilide began to be used to treat disease. At the same time, Ferdinand Blumenthal described... 

Table 2 Major organoarsenic drugs in the treatment of syphilis...

The toxicity of arsenic has been put into practical use in medicine. Ehrlich in 1909 developed Salvarsan, the trade name for arsphenamine (1), which was the first modem chemotherapeutic agent effective in the treatment of syphilis, which was eventually phased out by better organoarsenicals and latter by penicillin. Some specialist arsenical dmgs are still the treatment of choice for amoebic infections like glycobiarsol (2). ... 

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