PANTOTHENIC ACID 



stimulate the growth of Acetobacter suboxydans, as did pantoyltaurine 

 which was hydrolysed, liberating pantoic acid, which the organism 

 utilised. 2^ 



Although pantoyltaurine was a powerful inhibitor of bacterial 

 growth in vitro, the results of in vivo tests were disappointing ; rats, 

 however, were protected from the effects of haemolytic streptococci by 

 giving frequent large doses (see page 382). As already explained, the 

 failure of pantoyltaurine to exert a more pronounced chemothera- 

 peutic effect was due ultimately to the antagonistic action of the 

 pantothenic acid present in the blood of the animals, but the condition 

 was undoubtedly aggravated by the rapid elimination of the substance 

 in the urine ; this necessitated the giving of frequent injections in 

 order to maintain the blood concentration at a sufficiently high level. 

 Attempts to prepare derivatives of pantoyltaurine that might be 

 excreted less readily, have therefore been made. J. W. Barnett ^^ 

 prepared N-pantoyl-j3-aminoethylthiol, bis-(pantoyl-jS-aminoethyl) 

 monosulphide, disulphide, sulphoxide and sulphone, which were 

 tested on L. arabinosus and Strep, haemolyticus.^'^ None of the com- 

 pounds was more active than pantoyltaurine, but the disulphide and 

 the thiol were almost equally active and their effects were reversed by 

 pantothenic acid. The antibacterial index of the disulphide and of 

 the sulphone was 40,000 against Strep, haemolyticus. They had no 

 in vivo activity against Strep, haemolyticus in rats. Three aryl sub- 

 stituted analogues of pantoyltaurine, namely, j3-(a)/-dihydroxy-j3^- 

 dimethylbutyramido)-a-phenylethane sulphonic acid, j8-(ay-dihydroxy- 

 j3j3-diphenylbutyramido) -ethane sulphonic acid and j8-(a-tosyl-)/-hy- 

 droxy-/S/8-dimethylbutyramido) -ethane sulphonic acid, were prepared 

 by Barnett et al.,^^ but had neither in vitro nor in vivo activity. 



A further series of compounds, some of which were tested by 

 H. Mcllwain and D. E. Hughes,^' was prepared by Madinaveitia et 

 al.^^ These were pantamide, panthydrazide, N-(/3-diethylaminoethyl)- 

 pantamide, N-(5-diethylamino-2-pentyl)-paixtamide, N-pantoyl- 

 phenylalanine, N-pantoyl-hexahydroanthranilic acid, N-pantoyl- 

 nipecotic acid, ^-(N-pantoylaminoethyl)-^-tolylsulphone, j8-(N- 

 pantoylaminoethyl)-^-aminophenyl sulphone, ^-(N-pantoylamino- 

 ethyl)-^-methoxyphenyl sulphone, and N-pantoyl-;^-anisidine. In 

 this series the pantoyl group was combined with other radicals 

 associated with chemotherapeutic activity. However, the only com- 

 pounds that showed striking anti-bacterial activity when tested 

 against L. helveticus were panthydrazide and, to a smaller extent, pant- 

 amide. The former had no therapeutic action, however, on rats 

 infected with Strep, pyogenes, but the amide derived from 4-amino- 

 phenyl-/3-aminoethyl sulphone showed slight therapeutic activity 

 under these conditions. According to Mcllwain and Hughes, pant- 



398 



