p-AMINOBENZOIC ACID 525 



most effective compound, p-aminosalicylic acicl, inhibited growth of the 

 tubercle bacillus at concentrations as low as 1.5 y per cc. At this concen- 



NH 2 



-p-amino salicylic acid 



tration the inhibitor was bacteriostatic rather than bactericidal. The 

 compound fed at a concentration of 5 per cent of the diet was not toxic 

 for rats, mice or rabbits, but guinea pigs became emaciated, lost hair 

 and died within two weeks on such a diet. In guinea pigs infected with 

 Mycobacterium tuberculosis, the analogue tended to retard the disease, 

 but only at concentrations at which some of the animals died. However, 

 no toxic manifestations on administration of 10 to 15 g daily were ob- 

 served in patients with tuberculosis. Patients responded with a prompt 

 fall in temperature, improvement in general condition, gains in weight 

 and appetite, and increases in red cells and hemoglobin. 



p-Aminosalicylic acid in vitro is a very effective bacteriostatic agent 

 at concentrations of 0.1-1.5 y per cc for tubercle bacillus, 404-411 but does 

 not have appreciable inhibitory activity against other microorgan- 

 isms. 408 - 412 - 413 



In the presence of 1 y per cc of p-aminobenzoic acid, the amount of 

 p-aminosalicylic acid necessary for inhibition of growth of Mycobac- 

 terium tuberculosis H37Rv is increased approximately 16 fold. 42 Salicylic 

 acid also prevents the toxicity of ^-aminosalicylic acid in a somewhat 

 competitive manner, but is only 2-6 per cent as effective as p-amino- 

 benzoic acid. 395 



Contrasting with the inhibitory action on Mycobacterium tuberculosis, 

 ^-aminosalicylic acid replaces p-aminobenzoic acid in stimulating the 

 growth of two mutant strains of Escherichia coli which require p-amino- 

 benzoic acid for growth. 28 The analogue depending upon the testing con- 

 ditions is from 4 to 16 per cent as effective as p-aminobenzoic acid. 28 It 

 appears that ^-aminosalicylic acid inhibits the utilization of p-amino- 

 benzoic acid for tubercle bacilli, but is utilized in place of the vitamin 

 by Escherichia coli. Such activity, if general among microorganisms, 

 would account for the unusual specificity of p-aminosalicylic acid as an 

 inhibitory analogue. 



Strains of tubercle bacilli which are resistant to streptomycin are 

 sensitive to ^-aminosalicylic acid, 42, 407 and the two compounds have been 



