632 THE BIOCHEMISTRY OF B VITAMINS 



mice infected with Streptococcus hemolyticus C203 were D-pantoyltaur- 

 amido-4-chlorobenzene and D-pantoyltauramido-3,5-dibromobenzene. 

 However, only limited concentrations of these two compounds were found 

 to be reversed by pantothenic acid. This afforded an interesting compari- 

 son of the relative activities of analogues of d- and L-configuration. The 

 concentration of L-pantoyltauramido-3,5-dibromobenzene necessary for 

 inhibition of growth was found to be essentially equal to the lowest con- 

 centration of the D-form which pantothenic acid did not competitively 

 reverse. Also, L-2-(pantoyltauramido) pyridine was inactive at a ratio of 

 inhibitor to pantothenic acid of 6400, while the inhibition index of the 

 compound of D-configuration was 100. Hence, the analogues of L-con- 

 figuration appear to be inactive as competitive antagonists of pantothenic 

 acid. 



These pantoyltauramide derivatives also have antiplasmodial activity 

 in blood, but not in sporozoite-induced infections of Plasmodium gal- 

 linaceum in chickens. This suggests that the blood phases of this infection 

 require pantothenic acid. The tissue phases either may not require the 

 vitamin or may obtain sufficient supplies of pantothenic acid or other 

 agents in the tissues to prevent the inhibitory action of the pantothenic 

 acid analogues. The most active analogue is D-pantoyltauramido-4-chloro- 

 benzene, which is four times as active as quinine in a standard four-day 

 trophozoite-induced infection (in brackets in Table 27), or sixteen times 

 as active in a more sensitive test where the peak parasitemias were not 

 reached until seven days after infection. The suppressive action of the 

 analogues was completely prevented by addition of adequate quantities 

 of pantothenic acid to the diet. 



The pantoyltauramides were found to be toxic for chicks, but only at 

 concentrations well above those required for therapeutic doses. 69 At a 

 concentration of 0.5 per cent in the diet, D-pantoyltauramido-4-chloro- 

 benzene reduced food intakes markedly and caused death of birds after 

 the twelfth day. At concentrations of 0.1 per cent, the analogue caused 

 only slightly reduced weight gains in a ten day period, and 0.025 per cent 

 (40 mg/kg/day) of the analogue did not affect growth of the chicks. The 

 toxicity of even 0.5 per cent of the analogue in the diet was prevented by 

 supplementation of 0.025 per cent of calcium D-pantothenate. An increase 

 was obtained in immature erythrocytes which was directly related to the 

 size of the dose of the analogue and length of treatment, although there 

 was no effect on the total erythrocyte count. Concentrations in the diet 

 as low as 0.0067 per cent gave significant increases in immature erythro- 

 cytes in ten days. However, rats receiving 0.25 g/kg/day of the analogue 

 maintained a normal blood picture even after 30 days of treatment. 

 Pantoyltauramidobenzene, pantoyltauramido-5-bromobenzene, pantoyl- 



