METABOLITE ANALOGUES 115 



synthesis of the amide from the acid. Many examples of 

 this growth factor antagonism have now been worked out and 

 some are given in Table XI. There is one difference between 

 these examples and that of sulphanilamide, in that whereas the 

 latter is effective against many organisms whether these are 

 nutritionally exacting towards ;p-amino-benzoic acid or not, 

 the nutritional antagonists are effective as growth inhibitors 

 only in those cases where the organism tested is nutritionally 

 exacting towards the factor concerned. Whether this is a 

 difference of principle or degree remains to be seen. 



The main interest of this type of work was that it gave 

 promise of the rational development of chemotherapeutic 

 agents. Many nutritionally exacting organisms are patho- 

 genic, and if it were possible to prevent their growth 

 in vivo by nutritional antagonism, then the growth factor 

 analogues might form a valuable source of chemotherapeutic 

 agents. Pantoyl-taurine is effective as a bacteriostatic agent 

 against streptococcal infections in the rat and is antagonised 

 by pantothenic acid. So far, however, no marked advances 

 in the chemotherapeutic field have come from this research 

 for three main reasons : most of the antagonists so far prepared 

 are simple molecules, and are excreted too rapidly to be 

 effective m vivo ; the internal environment of the host contains 

 such quantities of the .natural growth factor that the com- 

 petitive amounts of analogue that must be injected 9,re 

 unreasonably large; and in some cases the effect of the 

 analogue is to deprive the host of the metabolism associated 

 with the growth factor as well as the organism (e.g. the adminis- 

 tration of pyrithiamin to rats gives rise to the symptoms of 

 vitamin Bj deficiency). 



