p-AMINOBENZOIC ACID 521 



Resistant strains of pneumococci did not lose type-specific characteris- 

 tics, and were still susceptible to anti-serum. 303 



Sulfonamide-resistant strains of pneumococci 26e produce less hydrogen 

 peroxide than the parent strain, and the ability to form hydrogen peroxide 

 is lost by strains of a-streptococci which become resistant to sulfathi- 

 azole; 349 but these strains no longer require riboflavin for growth and are 

 more effective than the parent strain in oxidizing a number of sub- 

 strates. 349 This contrasts to resistant strains of pneumococci, which are 

 less effective in oxidizing glycerol, lactate and pyruvate but not glucose. 266 

 Strains of Shigella with the greatest fermentation activity are more 

 resistant to sulfonamides. 325 Resistant strains of Mycobacterium ranae 38 ° 

 produce diazotizable arylamines. Development of resistance and increased 

 arylamine formation in Staphylococcus aureus is reported not to be asso- 

 ciated, but the arylamine in this case is apparently derived from trypto- 

 phan, and is not p-aminobenzoic acid. 375 



Other Inhibitory Analogues of p-Aminobenzoic Acid 



Shortly after the discovery of the competitive relationship of p-amino- 

 benzoic acid and the sulfonamides, many compounds differing from the 

 sulfonamides but related in structure to p-aminobenzoic acid were pre- 

 pared and tested. The compounds of this group which inhibit the utiliza- 

 tion of p-aminobenzoic acid by various organisms are indicated in Table 

 10. It is apparent that neither a free amino nor an acidic radical is essen- 

 tial for the inhibitory action of an analogue of p-aminobenzoic acid. 

 Nitro and acetamido groups may replace the amino group for certain 

 inhibitory analogues, while the modification of the carboxyl group can 

 be extended to a variety of changes. Utilization of carboxamide, ketone 

 and alcohol groups, as well as arsonic, phosphonic and phosphonous acid 

 groups in place of the carboxyl group of p-aminobenzoic acid and related 

 analogues results in some instances in inhibitory analogues. Some in- 

 hibitory analogues contain an isosteric, heterocyclic ring in place of the 

 aromatic ring structure of p-aminobenzoic acid, while other inhibitory 

 analogues are substituted p-aminobenzoic acids. Of a large number of 

 analogues of p-aminobenzoic acid with substituents in the aromatic 

 nucleus, only a few inhibit the utilization of this vitamin. 16, 21 Usually 

 disubstituted p-aminobenzoic acids are inactive, indicating the possibility 

 that one side of the ring structure of the vitamin must be intact for com- 

 bination with the appropriate enzymes. 



Halogeno-4-aminobenzoic Acid. Although 2-fluoro-4-aminobenzoic acid 

 is approximately one-third as effective as p-aminobenzoic acid in promot- 

 ing growth of certain organisms and in preventing the toxicity of sulfanil- 

 amide (p. 484), 3-fluoro-4-aminobenzoic acid is almost as effective as 



