Chapter MID 



p-AMINOBENZOIC ACID 



The discovery by Woods 1 in 1940 that p-aminobenzoic acid, first 

 synthesized by Fischer 2 in 1863, is an essential metabolite was not the 

 result of nutritional studies, but was made on the basis of the ability of 

 the factor to prevent the bacteriostasis of sulfanilamide and related com- 

 pounds. Even the evolvement of the sulfonamides and related compounds 

 as chemotherapeutic agents was almost as novel, particularly since sul- 

 fanilamide had been synthesized by Gelmo 3 in 1908, approximately a 

 quarter of a century before the chemotherapeutic action of this type of 

 compound was discovered. 



The inhibitory activity of many dyes against bacteria in vitro led to 

 the preparation of a number of azo compounds including those in which 

 diazotized sulfanilamide was coupled with a number of aromatic amines 

 and related compounds. 4, 5 The activity of one of these compounds, pron- 

 tosil, 6 attracted widespread attention because of its effectiveness in vivo, 



NH 2 

 ICl-HjN— f ?— N=N— <f ?— £ 



prontosil 



particularly against staphylococcal and /^-hemolytic streptococcal sep- 

 ticemia. 7 However, the compound was inactive in preventing the growth 

 of these bacteria in vitro. Also, it was found that a number of active 

 compounds could be prepared by coupling diazotized sulfanilamide with 

 a variety of aromatic amines and phenols; but the sulfanilamide portion 

 of the molecule was highly specific, since a wide variety of other diazo- 

 tized amines did not form active compounds on coupling with these same 

 aromatic amines and phenols. 8 The specificity of sulfanilamide in the 

 synthesis of active azo derivatives and the fact that the azo compounds 

 were not effective in vitro led to the discovery that sulfanilamide was 

 fully active in replacing prontosil. 8 Reduction of the azo group in vivo 

 apparently allows the formation of the active principle, which is also 

 active in vitro. 



Studies of the mechanism of the bacteriostasis produced by sulfanila- 



481 



