p-AMINOBENZOIC ACID 511 



dine, 225 - 226 thiourea, 225 - 226 urethane, 215 - 21C - 223 asparagine, 217 hexyl carba- 

 mate, 227 6-benzylthiouracil, 228 5,6-tetramethylene thiouracil, 228 O-ethyl- 

 isourea, 224 dicyandiamide, N-methyl thiourea, 224 penicillin, 229 and 

 n-propyl, isopropyl, n-butyl and isobutyl carbamates. 230 



Although the synergism of sulfonamides with urea has been con- 

 firmed, 231 - 232 failures to confirm the synergism have also been reported. 233 

 Actually either additive or synergistic activity may be observed depend- 

 ing upon the experimental conditions employed. 



Ethyl carbamate is reported to exert an antisulfonamide effect on 

 luminous bacteria, 234 and a slight effect on the toxicity of sulfanamide 

 for Streptococcus hemolyticus 235 and Escherichia coli. 23r> 



The bacteriostatic activity of sulfathiazole is reported to increase with 

 temperature above 37° C for Escherichia coli and for Streptococcus 

 pyogenes. 236 p-Aminobenzoic acid becomes less effective in preventing 

 the toxicity of sulfathiazole and becomes a more potent inhibitor itself 

 at higher concentrations under these temperature conditions. 236 



Biological Effects of Sulfonamides and Related Compounds 



Effect of Biochemical Transformation. The effect of methionine, 

 purines (or derivatives), serine or thymine (or derivatives, e.g., thymi- 

 dine) in preventing the toxicity of sulfonamides are discussed separately 

 (pp. 469 and 473). The involvement of p-aminobenzoic acid and related 

 catalytic factors in the biosyntheses of these factors is indicated by the 

 results of such inhibition studies. 



The possibility that p-aminobenzoic acid has a role in the biosynthesis 

 of other metabolites has been indicated by the ability of certain metab- 

 olites to exert an effect on the toxicity of sulfonamides. For example, 

 arginine, histidine, lysine, methionine, glutamic acid and aspartic acid 

 are reported to have some ability to prevent the toxicity of sulfonamides 

 for Proteus vulgaris. 287 Valine, and to a lesser extent lysine and isoleucine, 

 prevent the toxicity of sulfanilamide for Escherichia coli in a medium 

 containing methionine, purines, serine and either thymine or folic acid. 238 

 Tryptophan has some ability to prevent the toxicity of sulfathiazole for 

 Staphylococcus aureus. 239 ' 240 



Various sulfonamides inhibit the growth of Eremothecium ashbyii, and 

 the inhibition is paralleled by a decrease in formation of flavin, pre- 

 sumably riboflavin. 241 



The phosphorus content of yeast is increased by growth in the presence 

 of sulfanilamide (200 y per cc) from 1.9 to 2.6 mg per g of dry cells. A 

 slight increase in the nitrogen content is also noted under similar condi- 

 tions; p-aminobenzoic acid (1 y per cc) counteracts these effects. 134 - 242 



