ANALOGUES 



hyrazide and pantamide had antibacterial indices of 4000 and 20,000 

 respectively against Strep, haemolyticus. 



As pantothenic acid is the only growth factor known to be essential 

 for Plasmodium, ^^°' Mead et al}^^ tested the activity of ^-pantoyltaurine 

 and several of its derivatives in malaria ; ^-pantoyltauramide was 

 found to be active in vivo. This observation has resulted in a large 

 member of N-substituted pantoyltauramides being made but, although 

 pantoyltauramido-4-chlorobenzene was four to sixteen times as effective 

 as quinine in P. gallinaceum infections in chicks, none of the compounds 

 appears to have any clinical value. ^^^ The antimalarial effect of pan- 

 toyltauramide was neutralised by one-quarter of its weight of pan- 

 tothenic acid ; ^^^ and this may explain the disappointing results 

 obtained with antimalarials of this type. 



Many sulphur-free analogues of pantothenic acid have been found 

 to inhibit the growth of bacteria. Thus, y-hydroxy-w-butjryl-jS- 

 alanine and y-hydroxy-w-valeryl-jS-alanine were inhibitory to 5. 

 haemolyticus and C. diphtheriae, but the effect was not reversed by 

 pantothenic acid.^^» ^^ They also inhibited the growth of E. coli, 

 Proteus vulgaris and Staph, aureus, which are not inhibited by pantoyl- 

 taurine and which are capable of synthesising pantothenic acid. 

 With E. coli the inhibitory effect was not prevented by the addition 

 of pantothenic acid, but inhibition by the hydroxybutyryl derivative 

 was partially reversed in the case of Pr. vulgaris. Thus, inhibition by 

 these particular compounds would appear to be of the non-competitive 

 type, but associated in some way, as yet undisclosed, with pantothenic 

 acid. 



As already mentioned (see page 396), a- and j8-methylpantothenic 

 acid ^^' ^^ inhibited bacterial growth, as did several other pantoyl 

 amino acids. For Streptohacterium plantarum, ^-methylpantothenic 

 acid (pantoyl-j3-aminobutyric acid) had an anti-bacterial index of 

 200,^^ whilst the values for other organisms were : ^^ for Lactobacillus 

 helveticus, 250 ; for L. arabinosus, 1500 ; for Leuconostoc mesenteroides , 

 2000 ; and for Lactobacillus fermenti , 5000. This last-named organism 

 is particularly resistant to pantoyltaurine and pantothenyl alcohol. 

 Pantoyl-isoserine and pantoyl-j3-amino-isobutyric acid were less effec- 

 tive, the corresponding antibacterial indices being : 1000 and 2500 ; 

 1000 and 2500 ; 1000 and 5000 ; and > 50,000 respectively. In 

 some instances, complete inhibition was not obtained, the reason 

 being apparently that at these high concentrations they acted as 

 growth stimulants. A homologue of pantothenic acid, N-(ay- 

 dihydroxy-/SjS-dimethylvaleryl)-^-alanine, inhibited the growth of 

 lactic acid bacteria and the inhibition was reversed by pantothenic 

 acid.^^ Rather surprisingly, the taurine analogue was less active 

 than the ^-alanine derivative. *i" 



399 



