496 THE BIOCHEMISTRY OF B VITAMINS 



sive lists of these compounds together with their activities. Consequently, 

 only these compounds which have been studied with respect to their rela- 

 tionship to p-aminobenzoic acid are included in this monograph. 



Sulfonamides, Sulfones and Related Analogues: Activity and Reversals 

 with p-Aminobenzoic Acid in Vitro 



After the appearance of the report of Woods 1 indicating the competi- 

 tive interrelationship of p-aminobenzoic acid and the sulfonamide drugs, 

 this effect was confirmed by many others, and the effect of p-aminoben- 

 zoic acid on the toxicity of related inhibitory analogues was determined 

 for a wide variety of organisms. The organisms for which the toxicity of 

 sulfanilamide, sulfathiazole or sulfapyridine in vitro is prevented by 

 p-aminobenzoic acid are indicated in Table 4. It is apparent that numer- 

 ous species of bacteria, fungi, higher plants, diatoms, yeast and flagellates 

 are inhibited by these sulfonamides, and the inhibition is prevented 

 competitively by p-aminobenzoic acid. Similar results have been obtained 

 with a large number of N 1 -substituted sulfanilamides, sulfones, sulfoxides 

 and similar compounds structurally related to p-aminobenzoic acid 

 (Table 5). 



As indicated in these tables, the inhibition indices of an individual 

 inhibitor vary considerably for different organisms. Also, organisms 

 which require folic acid for growth are highly resistant to inhibition by 

 any of the analogues of p-aminobenzoic acid. However, the relative 

 efficiencies of the different sulfonamides in inhibiting the growth of various 

 organisms are rather consistent, and it has been suggested that there is 

 no specificity in the ability of sulfonamides to inhibit specific organ- 

 isms. 100 While this is true for most organisms, there are many exceptions. 

 For example, sulfathiazole and sulfapyridine are only slightly more 

 effective for Streptobacterium plantarum than sulfanilamide, and bis- 

 (4-aminophenyl)sulfone, which is only slightly more effective for 

 Escherichia coli than sulfanilamide, is fifty times as efficient as sulfanila- 

 mide for Mycobacterium tuberculosis. The sulfone is more active than 



NHr-/ Y-SO2-/ ^>-NH 2 



bis (4-aminophenyl) sulfone 



sulfathiazole for Streptobacterium plantarum, while sulfathiazole is con- 

 siderably more effective than the sulfone against Escherichia coli. Even 

 though the order of the relative activities of sulfanilamide, sulfapyridine 

 and sulfathiazole is the same for essentially all organisms, there is little 

 difference in their inhibitory ability against organisms such as Saccha- 



