From Dyes to Sulfonamides The First Antibacterials

One of the problems with these early endeavours was the lack of reproducible and reliable antibacterial tests. With a view to extending the search for broad-spectrum antibacterial agents, I.G. Farbenindustrie in Elberfield (also owners of the Hoechst Dyeworks) appointed Gerhard Domagk to 

A few isolated clinical trials of the drug took place in Germany during the period 1933-1935, and Domagk wrote a number of reports about his discoveries but the first serious clinical trial was carried out in 1936 at Queen Charlotte s Maternity Hospital in London. Here, Leonard Colebrook was trying to reduce still further the number of deaths from puerperal fever (which then stood at 2-3 per 1000 deliveries). Initially, he treated 38 women who were very seriously ill with streptococcal infections and saved the lives of all but three of them. Normally, at least 25% of these patients would have died. His Lancet paper generated considerable interest, as did a subsequent trial with a further 26 women, all of whom were saved. 

Despite this setback, the pharmaceutical industry was encouraged to prepare literally hundreds of sulfonamides, of which May and Baker 693 (sul-fapyridine) proved to be the most potent and broad spectrum. It also achieved star status once it was revealed that it had been used to save the life of Winston Churchill when he contracted pneumonia during a visit to North Africa in December 1943. Other sulfonamides that have been widely prescribed are sulfadiazine, sulfadimidine (especially for urinary tract infections and meningitis caused by meningococcal infections) and sulfamethoxazole. One problem with many sulfonamides is their relative water insolubility and their tendency to crystallise in the kidney tubules. They are also metabolised via acetylation of the aniline nitrogen, and these metabolites are both inactive and less soluble. 

As for Gerhard Domagk, he received due recognition for his discovery with the award of the Nobel Prize for Physiology or Medicine in 1939, although, due to the exigencies of the Second World War, he was unable to 

I am continuing to work in the field of chemotherapy, although I know that in all probability I will never be able to help as many people who will possibly be annihilated by a single atom bomb. 

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