500 THE BIOCHEMISTRY OF B VITAMINS 



benzoic acid. 184 The treatment with the sulfoxide does not affect the 

 immunization of the animal against the endotoxin or the organism. 184 

 Similar results were obtained with endotoxin from a particularly virulent 

 strain of Escherichia coli. 18 * 



Inhibitions by Sulfonamides Unaffected by p-Aminobenzoic Acid 



Sulfapyrazine, sulfadiazine and sulfathiazole inhibit completely the 

 growth of Bacterium tularense, but p-aminobenzoic acid does not affect 

 the inhibition. 113 Although such cases are unusual for these analogues, 

 there are a number of sulfonamide derivatives related structurally to 

 p-aminobenzoic acid which are inhibitory, but the inhibition is not re- 

 versed by p-aminobenzoic acid. The toxicity of 2-, 3-, 5- and 7-sulfanila- 

 midoindazoles for Brucella melitensis is only slightly reversed by 

 p-aminobenzoic acid. 1S5 3',5'-Dibromosulfanilanilide is strongly inhibitory 

 to numerous strains of pneumococci, hemolytic streptococci and staphy- 

 lococci, but is only slightly inhibitory to Friedlanders' bacillus, Escher- 

 ichia coli, Pseudomonas aeruginosa and various types of dysentery bacilli. 

 However, the strong inhibition observed with the gram-positive cocci is 

 not prevented by p-aminobenzoic acid, but this vitamin reverses the 

 slight inhibition obtained with the gram-negative bacilli. 186 Similarly, 

 the toxicity of a series of 3',4'- and 3',5'-halogenosulfanilanilides is also 

 unaffected by p-aminobenzoic acid for certain organisms. 187, 188 The tox- 

 icity of p-aminomethylbenzenesulfonamide is not affected by p-amino- 

 benzoic acid or by p-aminomethylbenzoic acid for a wide variety of 

 organisms. 189, 190 



For some organisms the toxicity of sulfanilamide is only partially 

 counteracted by p-aminobenzoic acid. This is true of onion rootlets, for 

 which p-aminobenzoic acid is toxic at higher concentrations. 149 Although 

 very effective at low concentrations in preventing the toxicity of sul- 

 fanilamide, p-aminobenzoic acid is toxic at higher concentrations for pea 

 roots. 150 A similar situation exists with flax seed, which germinates slowly 

 or not at all in the presence of relatively high concentrations of sulfanil- 

 amide, and the growth of the seedlings is retarded by lower concentra- 

 tions of the drug. Although p-aminobenzoic acid counteracts the inhib- 

 itory action, root development is not quite restored to normal. Higher 

 concentrations of p-aminobenzoic acid are toxic. 148 For Lupinus albus 

 seedlings 191 p-aminobenzoic acid enhances the toxicity of sulfanilamide. 



In systems in which the toxicity of sulfonamides or related compounds 

 is not affected by p-aminobenzoic acid, it appears that in most instances 

 enzymatic reactions other than those concerned with the utilization of 

 p-aminobenzoic acid are involved. This does not preclude the possibility 

 that in some instances a sequence of two reactions is prevented by the 



