CHEMOTHERAPY 131 



Bacterial Infections. — Until 1935, apart from the 

 local application of acridine dyes, such as acriflavine 

 and proflavine, to wounds and surface lesions, developed 

 during the 1914-1918 war, the only bacterial disease 

 Avhich had shown itself susceptible to chemotherapy 

 was a pneumococcal infection of mice which responded 

 to treatment with optoquin, ethyl hydrocupreine, 



CH 



CHa 



CH.CH2.CH3 



CHj, 



I II I \L 



N ^^ 



which is also active against trypanosomes. 



In 1935 Domagk subjected to clinical trial the drug 

 prontosil, sulphonamido-chrysoidin, 

 NHo 



.N=N/ \SO2.NH2, ^^hich had been 



discovered by Klarer and Mietzsch in 1932, and found 

 that it was an effective agent against streptococcal 

 infections, in spite of the fact that it was inactive in 

 vitro. This phenomenon was explained by Trefouel, 

 Trefouel, Nitti and Bovet in 1935, who showed that 

 prontosil was broken down in the body to /)-aminobenzene 

 sulphonamide, now known as the drug, sulphanilamide, 



which was active both in vitro 



and in vivo. This discovery led to a tremendous amount 

 of research for similar and improved drugs. Some 

 2,500 derivatives of sulphanilamide have been syn- 

 thesised, most of them by substitution on the nitrogen 

 atoms. In nomenclature the sulphonamide group — 



