524 THE BIOCHEMISTRY OF B VITAMINS 



sulfanilamide in preventing the growth of Escherichia coli, and 2-chloro- 

 4-aminobenzoic acid is more active than sulfanilamide against Escherichia 



COOH 



NH 2 NH 2 



2-ch!oro-J+-aminobenzoic acid 3-fluoro-^-aminobenzoic acid 



coli. 21 However, in the presence of methionine, 2-chloro-4-aminobenzoic 

 acid not only does not exert an inhibitory effect on Escherichia coli but 

 has a slight ability to prevent the toxicity of sulfanilamide for that 

 organism. The 2-chloro derivative also has some ability to prevent the 

 toxicity of sulfonamides for Diplococcus pneumoniae, Streptococcus 

 pyogenes and Streptococcus hemolyticus. 16 ' 32, 33 Strains of Escherichia 

 coli which are resistant to inhibition by 2-chloro-4-aminobenzoic acid are 

 obtained in a single transfer in the presence of the analogue; however, 

 these strains resistant to 2-chloro-4-aminobenzoic acid are not resistant 

 to sulfonamides, but sulfonamide-resistant strains are resistant to inhi- 

 bition by the 2-chloro derivative. 400 



Pantothenic acid is reported to be as effective as p-aminobenzoic acid 

 in preventing the toxicity of 2-chloro-4-aminobenzoic acid; 401 however, 

 since this effect is not observed after short incubation periods 402 and 

 since resistance 400 to the inhibition occurs after a longer incubation 

 period in the absence of pantothenic acid, it appears that this effect may 

 be associated with the resistance phenomenon. Either thiamine or glu- 

 tamic acid exerts effects analogous to pantothenic acid on this inhibi- 

 tion. 402 



In contrast to slight growth-promoting activity of 2-bromo-4-amino- 

 benzoic acid, 21 ' 33 which may possibly be attributed to contamination 

 with p-aminobenzoic acid, 3-bromo-4-aminobenzoic acid has some in- 

 hibitory action against Escherichia coli and Streptococcus hemolyticus 

 Group A. 16 3-Chloro-4-aminobenzoic acid is somewhat more inhibitory 

 than the corresponding 3-bromo derivative for Escherichia coli. The 3- 

 chloro derivative is also effective against Streptococcus pyogenes. 



4-Amino-2-hydroxybenzoic Acid (^-Aminosalicylic Acid) and Related 

 Analogues. Since benzoic and salicylic acids were reported to stimulate 

 the oxygen consumption and carbon dioxide production of tubercle ba- 

 cilli, 403 Lehmann, 404, 405 in attempting to find an inhibitor of the stimula- 

 tory action, tested 60 substances of similar structure and found that the 



