Metal Complexes in Tumor Therapy

Abstract

The history of medicine shows that metal compounds have been extensively used in medical therapy. For example, antimony compounds were used as emetics and in tropical disease treatment, whereas bismuth compounds were widely applied as astringents and dermatological antiseptics. Arsenic derivatives were used in asthma, tuberculosis, leprosy and dermatoses (arsenic occurs in nature as a non-metal in anionic form and also as a metal in cation-ic form). By spreading of syphilis in Europe towards the end of the fifteenth century, the application of arsenic widened considerably. The greatest sensation was the discovery of salvarsan, Figure 10.1.1, which was prepared in 1909 by Paul Ehrlich,* a German chemist and bacteriologist, in collaboration with A. Bertheim, also a German chemist. They ascribed the formula shown in Figure 10.1.1 to salvarsan, 4,4′-arsenobis(2-aminophenol)dihydrochloride, but later on the X-ray structure analysis showed that the active compound was a cyclic trimer with six arsenic atoms in the ring, the two aminophenol molecules bound to every arsenic atom. In 1910, with his colleague Sahachiro Hata, Ehrlich conducted tests in combating syphilis. His preparation 606, later called salvarsan, was very effective and harmless despite a high arsenic content. Ehrlich called salvarsan a “magic bullet” because a single injection was sufficient. In fact, Ehrlich prepared 914 compounds similar to salvarsan, of which salvarsan was the most promising in the chemotherapy of syphilis.¹