630 THE BIOCHEMISTRY OF B VITAMINS 



respectively, for 9 days' incubation in vitro. G5 The phenyl sulfide is also 

 effective in vitro against Trichomonas foetus and Trichomonas gallinae. 

 However, even at high concentrations, it did not affect Trichomonas 

 vaginalis infection in monkeys and human beings. 



The phenyl sulfide has been reported to have an extremely low acute 

 and chronic oral toxicity in several animal species, 06 and local irritation 

 effects are not obtained even upon repeated administration. An anemia 

 developed in monkeys which gradually disappeared upon discontinuing 

 the administration of the compound. Smooth muscle was generally stimu- 

 lated by the analogue. 



DL(N-Pantoyl-/?-aminoethyl) p-tolyl sulfone and the corresponding 

 p-aminophenyl and p-methoxyphenyl sulfones inhibited competitively 

 the functioning of pantothenic acid in Lactobacillus casei with inhibition 

 indices of approximately 6400, 6400 and 1600, respectively. Streptococcus 

 pyogenes was also inhibited by these compounds, but only a slight chemo- 

 therapeutic effect was obtained in experimental streptococcal infections 

 in rats. 



Substituted Pantoyltauramides. Since pantoyltaurine and its amide 

 had been found to inhibit competitively the utilization of pantothenic 

 acid in a relatively large number of bacteria, many substituted amides 

 of pantoyltaurine were prepared as possible chemotherapeutic agents, 

 particularly against the malarial parasites and streptococci. The activities 

 of these compounds against Streptococcus hemolyticus C203 in vitro and 

 in infected mice and as suppressives against the malarial parasites in 

 chicks are shown in Table 27. Streptococcus viridans, Streptococcus 

 agalactiae, and pneumococci were also susceptible to this group of in- 

 hibitors. Sulfonamide-resistant streptococci were just as susceptible to 

 the substituted pantoyltauramides as the normal strains. 



It is interesting to note that the substituted amides are extremely effec- 

 tive inhibitors of the utilization of pantothenic acid in Streptococcus 

 hemolyticus C203. 70 The more active of the compounds are approximately 

 10 to 20 times as effective as pantoyltaurine in vitro. Also, the protective 

 activity of the substituted pantoyltauramides in experimental strepto- 

 coccal infections in mice is in contrast to the inability of pantoyltaurine 

 to exert any protective action for mice. Even the chemotherapeutic activity 

 of pantoyltaurine which was observed in rats was obtained only with 

 large doses administered frequently. 51 



All the substituted pantoyltauramides were relatively nontoxic to mice 

 and rats, and with most of the analogues both the chemotherapeutic 

 activity and in vitro inhibition of growth were prevented by higher con- 

 centrations of pantothenic acid. Of the compounds listed, the two most 

 effective in maintaining blood levels and exerting a protective action on 



