526 THE BIOCHEMISTRY OF B VITAMINS 



reported to act synergistically in inhibiting the growth of some strains 

 of the organism. 411 With other strains, only additive effects are ob- 

 served. 42, 414 Nevertheless, the utilization of ^-aminosalicylic acid con- 

 current with streptomycin to prevent the selection of resistant strains is 

 indicated. 



Although p-aminosalicylic acid is reported to have little therapeutic 

 activity in rabbits or guinea pigs infected with certain strains of tubercle 

 bacilli, 405, 408, 414 the analogue appears to suppress experimental tubercu- 

 losis in mice, 42 as determined by histopathologic examination. 41 "' The 

 effect of streptomycin on the analogue appears to be additive in vivo. 



^-Aminosalicylic acid is rapidly adsorbed and excreted by human sub- 

 jects as well as by laboratory animals. 414, 416419 Although blood levels of 

 the compound can be maintained in the animals for several hours, ap- 

 proximately 85 per cent of the administered dose is recoverable from the 

 urine within ten hours. 416 Recovery as conjugated amines was highest 

 (60 per cent of total dose) in man and apparently negligible in the dog. 410 

 Both the free ^-aminosalicylic acid and the N-acetyl derivative can be iso- 

 lated from the urine of rabbits after administration of p-aminosalicylic 

 acid. 417 In the urine of one human subject, three compounds containing 

 a free amino group and two conjugated amines have been detected subse- 

 quent to the administration of ^-aminosalicylic acid. 416 Among these, 

 unchanged p-aminosalicylic acid, p-aminosalicyluric acid and N-acetyl- 

 p-aminobenzoic acid have been identified. 416 



4-Amino-3-hydroxybenzoic acid is about one-third as effective as sul- 

 fanilamide against Streptococcus pyogenes, and has a slight chemothera- 

 peutic action in mice infected with that organism. 32 The corresponding 

 3-methyoxy derivative is somewhat less inhibitory to Streptococcus 

 hemolyticus Group A. 16 



Other Substituted p-Aminobenzoic Acids. Both 2, 4-diamino- and 

 3,4-diaminobenzoic acids are antagonists of p-aminobenzoic acid for 

 Diplococcus pneumoniae, 33 and compare favorably with sulfanilamide in 

 inhibiting the growth of Escherichia coli. 21 Considerable loss in activity 

 is observed 16 with acetylation of the 2-amino group of the former com- 

 pound. 16 



3-Methyl-4-aminobenzoic acid has some inhibitory activity against 

 Escherichia coli and Streptococcus hemolyticus. The corresponding 

 2-methyl derivative is less effective against Escherichia coli, and is inac- 

 tive against Streptococcus hemolyticus. The amide of the 3-methyl 

 derivative is less active than the parent compound. 



Isosteres. A number of compounds which are isosteric with p-amino- 

 benzoic acid are rather potent inhibitory analogues of the vitamin. 

 5-Nitrothiophene-2-carboxylic acid and the corresponding amide are more 



