Prontosil, drug discovery

The recent period of rapid progress began with the discovery of the sulfa drugs by G. Domagk. In 1935 Domagk discovered that tlu compound prontosil, a derivative of sulfanilamide, was effective in the control of streptococcus infections. It was soon found by other workers that sulfanilamide itself is just as effective in the treatment of these... 

Apart from the action of arsenobenzyl compounds in anthrax and that of certain drugs in the urinary tract, the chemotherapy of bacterial infections dates from 1935. I was present at the meeting in London in March of that year at which Horlein of Elberfeld announced the discovery of Prontosil. I am sure that no one there can have had any conception of the developments to which this would lead. Moreover, no one at the present day without a long memory can have much idea of what the practice of medicine and surgery was like before this discovery. Nowadays the vast majority of deaths are due to degenerative or malignant disease. Thirty years ago cancer was certainly one of the three major causes of death, but the others were pneumonia and tuberculosis, and it will be profitable to examine the effect of later developments on mortality from these two diseases. 

Prontosil is an effective antibacterial substance in vivo, that is, when injected into a living animal. Prontosil is not medicinally active when the drug is tested in vitro, that is, on a bacterial culture grown in the laboratory. In 1935, the research group at the Pasteur Institute in Paris headed by J.Tr fouel learned that Prontosil is metabolized in animals to sulfanilamide. Sulfanilamide had been known since 1908. Experiments with sulfanilamide showed that it had the same action as Prontosil in vivo and that it was also active in vitro, where Prontosil was known to be inactive. It was concluded that the active portion of the Prontosil molecule was the sulfanilamide moiety. This discovery led to an explosion of interest in sulfonamide derivatives. Well over a thousand sulfonamide substances were prepared within a few years of these discoveries. 

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