486 THE BIOCHEMISTRY OF B VITAMINS 



organisms the analogue is not particularly effective in replacing p-amino- 

 benzoic acid (Table 2). 



Alkyl esters of p-aminobenzoic acid are not readily hydrolyzed by 

 many organisms. Also, considerable variation in activities has been re- 

 ported in some cases. Thus, ethyl p-aminobenzoate is reported to be 

 from less than 0.1 per cent 19 to almost 100 per cent as effective as 

 p-aminobenzoic acid for Clostridium acetobutylicum. 11 



An ester such as diethylaminoethyl p-aminobenzoate (procaine) ap- 

 pears to be more readily hydrolyzed by various organisms than either 

 the methyl or ethyl esters. Since this and related compounds are widely 

 used as local anesthetics, the ability of these compounds to prevent 

 sulfonamide-induced bacteriostasis has received widespread atten- 

 tion. 30 - 40 ' 48<54 As indicated in Table 2, procaine is almost one-fourth as 

 active as p-aminobenzoic acid for Streptobacteriwn plantarum 26 and 

 Streptococcus hemolyticus. It is also utilized by Acetobacter sub oxy dans, 22 

 Clostridium acetobutylicum, 13, 17 ~ 20 Escherichia coli, M Staphylococcus 

 aureus, 110 Eberthella typhosa, Gi and pneumococci. 48 ' 63 The inhibitory 

 effect of sulfanilamide on sprouting wheat is decreased by a number of 

 local anesthetics derived from p-aminobenzoic acid. 59 



Different sulfonamides are similarly affected by procaine. The latter 

 compound has been reported to prevent the bacteriostasis resulting from 

 sulfanilamide, 50 - 53 > 61 - 63 sulfapyridine, 40 ' 48 sulfathiazole, 40 - 49 - 60 bis(p- 

 aminophenyl) sulfoxide, 49 bis (p-aminophenyl ) sulf one, 49 p-aminophenyl 

 p-hydroxyphenyl sulfone, 49 p-aminophenyl p-nitrophenyl sulfoxide, 49 and 

 prontosil. 62 



Other anesthetics containing p-aminobenzoic acid are also active. 

 y - Dimethy lamino - a, 8 - dimethylpropyl, y - diethy lamino - B, B - dimethyl- 

 propyl, /?-diethylaminoisohexyl and y-di-n-butylpropyl p-aminobenzoates 

 are 1-10, 0.1-1.0, 1.0 ca. and 0.1 ca. per cent, respectively, as effective as 

 p-aminobenzoic acid in preventing the toxicity of sulfapyridine for 

 Escherichia coli. 40 For Staphylococcus aureus, the first two compounds 

 are somewhat more than 1 per cent, and procaine approximately 10 per 

 cent, as effective as p-aminobenzoic acid in preventing the toxicity of 

 sulfathiazole. 40 y-Di-n-butylpropyl p-aminobenzoate is considerably less 

 active than procaine in preventing sulfanilamide bacteriostasis. 61 



Procaine is reported to be hydrolyzed by an esterase in human and 

 mouse blood. 50 The mortality of mice infected with streptococci and 

 treated with sulfanilamide is slightly greater when procaine is injected 

 with the sulfanilamide. 50, 53 The effect is significant only when maximum 

 nontoxic doses of procaine are administered. 53 The pneumococcal thera- 

 peutic action of sulfapyridine in mice is decreased by administration of 

 local anesthetics derived from p-aminobenzoic acid. 51 Procaine counter- 



