Chapter X 



^-AMINOBENZOIC ACID 



I. INTRODUCTION 



In 1932, F. Mietzsch and J. Klarer ^ synthesised the substance, 

 4-sulphonamido-2 ' : 4'-diammoazobenzene dihydrochloride to which 

 the name Prontosil rubrum was subsequently given : 

 NHa 



HaNf ^ : N< ^SOaNHg . 2HCI 



This compound was shown by G. Domagk ^ and others to kill haemo- 

 lytic streptococci in mice, although it had no activity in vitro. Trefouel 

 et al.^ prepared other azo compounds of a similar type, and noted that 

 the sulphonamide group appeared to be essential for antibacterial 

 activity. They suggested that all these compounds were reduced in 

 the body to ^-aminobenzene-sulphonamide or, as it is now universally 

 called, sulphanilamide 



and that this was the curative agent. Tests on this substance, first 

 prepared by P. Gelmo ^ in 1908, showed that it was in fact as active 

 as Prontosil against streptococci, but in striking contrast to Prontosil 

 it was highly active in vitro as well as in vivo.^ The presence of sul- 

 phanilamide in the blood of patients under treatment with Prontosil 

 was demonstrated by A. T. Fuller, ^ thus confirming the hypothesis of 

 Trefouel et al. 



The discovery of the highly potent antibacterial activity of sul- 

 phanilamide was of the greatest importance in medicine. In the first 

 place, it gave a new impetus to chemotherapy, for hitherto the search 

 for antibacterial substances that could safely be used on patients and 

 at the same time eliminate the infection had been singularly unsuccess- 

 ful ; indeed, the use of antiseptics such as acriflavine in the treatment 

 of wounds during the 1914-18 war had discredited chemotherapy 

 because they damaged the tissues surrounding the wound. Secondly, 

 it led to the preparation of thousands of derivatives of sulphanilamide, 

 several of which were shown to be either more potent than the parent 



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