p-AMINOBENZOIC ACID 529 



Analogues of p-Aminobenzoic Acid Containing Arsenic, Antimony or 

 Phosphorus. The sodium salt of arsanilic acid (p-aminobenzenearsonic 

 acid), which has been termed atoxyl, was one of the first compounds 

 found to have trypanosomacidal activity. The discovery of the activity of 

 p-aminobenzoic acid in preventing the toxicity of the sulfonamides for 

 bacteria prompted analogous research on arsanilic acid. The effect of 

 arsanilic acid in retarding the growth of Escherichia coli as measured by 

 oxygen consumption is counteracted by p-aminobenzoic acid. 45 With 

 some strains of the organism, complete inhibition of growth occurs, and 

 in one case the inhibition index for half-maximum growth has been found 

 to be approximately 15,000. 107 The analogue is only about 3 per cent as 

 effective as sulfanilamide. Methionine also prevents the toxicity of 

 arsanilic acid, as well as sulfonamides, for Escherichia coli. 107 



OH OH 



HO— PO 



NH 2 NH 2 



arsanilic acid phosphanilic acid 



The trypanosomacidal activity of arsanilic acid, which is attributed to 

 the formation of the arsenoxide, is not affected by p-aminobenzoic acid in 

 a test which renders Trypanosoma equiperdum noninfective for young 

 rats. 107 However, the chemotherapeutic action of arsanilic acid in Try- 

 panosoma equiperdum infections in mice is reported to be counteracted 

 by certain doses of p-aminobenzoic acid and sulfanilamide. 42121 These 

 results suggest the possibility that substances of analogous structure pre- 

 vent the conversion of arsanilic acid to the active form. Further evidence 

 for such possibilities is indicated by reports that relatively large amounts 

 of p-aminobenzoic acid prevent the toxicity for rats of otherwise lethal 

 doses of arsanilic acid and related arsonic acids. 422-425 However, p-amino- 

 benzoic acid apparently does not prevent the therapeutic effects of these 

 arsenicals against Trypanosoma equiperdum in rats. If p-aminobenzoic 

 acid is not administered within a few hours after the arsenical, it is not 

 effective in preventing the toxic manifestations of the drugs. 425 p-Amino- 

 benzoic acid is not particularly effective in preventing the toxic effects of 

 trivalent arsenicals, especially that of ra-amino-p-hydroxyphenylarsen- 

 oxide. 425 The effect of an otherwise lethal dose of neoarsphenamine is 

 counteracted by p-aminobenzoic acid in dogs. 426 The trypanocidal ac- 

 tivity of y-(p-arsenosophenyl) butyric acid both in vivo and in vitro is 



