628 THE BIOCHEMISTRY OF B VITAMINS 



growth rate which was less susceptible to increasing concentrations of 

 the inhibitor. 



Mcllwain 33 obtained resistant strains of Streptococcus hemolyticus and 

 Corynebacterium diphtheriae by serially subculturing the parent strains 

 in increasing concentration of pantoyltaurine. The strains of streptococci 

 which were resistant to pantoyltaurine were just as sensitive to sulfanila- 

 mide as the parent strain. Also, sulfanilamide-resistant strains were 

 found to be as susceptible to pantoyltaurine as the parent strain. The 

 resistant strains of streptococci retained their requirement for pantothenic 

 acid and did not appear to destroy pantoyltaurine; but the resistant 

 strains of diphtheriae bacilli were capable of utilizing /^-alanine instead 

 of pantothenic acid, whereas /3-alanine did not replace pantothenic acid 

 in the nutrition of the parent strain. Selection for strains of diphtheria 

 bacilli which could utilize ^-alanine was accomplished in the absence of 

 pantoyltaurine. These strains were resistant to bacteriostasis by pantoyl- 

 taurine. Proteus morganii, which normally is not sensitive to inhibition 

 by pantoyltaurine, was found to be inhibited by a mixture of salicylic 

 acid and pantoyltaurine under conditions in which the single components 

 of the mixture were inactive. A similar action was observed in both 

 normal and resistant streptococci. Pantothenic acid was effective in pre- 

 venting the toxic effects of the mixtures. Strains of Proteus morganii 

 have since been found which are susceptible to inhibition by pantoyl- 

 taurine with very high inhibition indices, approximately 200,000. 33 



Analogues Related to Pantoyltaurine. Pantoyltauramide and some of 

 its substituted derivatives, as well as sulfones, sulfoxides, sulfides, a 

 disulfide, and a mercaptan related to pantoyltaurine have been prepared. 

 The formulas and names are listed in Table 26. 



DL-N-Pantoyltauramide was found to be active against Streptococcus 

 hemolyticus, Diplococcus pneumoniae, and Corynebacterium diphtheriae, 

 the inhibition indices being 2000, 10,000-50,000, and 2000-10,000, respec- 

 tively. 46 Although it was less active than pantoyltaurine in vitro, and 

 against streptococcal infections in rats, D-N-pantoyltauramide admin- 

 istered to chicks intravenously in enormous doses (2 g or more per kg 

 per day) was found to exert a marked suppressive action upon the growth 

 of Plasmodium gallinaceum in chicks, but not in ducks. The antimalarial 

 activity in terms of quinine equivalents was 0.03. The inactivity of panto- 

 thenic acid analogues in ducks is caused by a difference in the host rather 

 than susceptibility of the organism, but this difference was not the result 

 of variations in the pantothenic acid content of the blood of the hosts. 

 The study of the antimalarial activity of analogues of pantothenic acid 

 was begun subsequent to the discovery that the addition of pantothenic 

 acid to an appropriate medium containing duck erythrocytes parasitized 



