THE FOLIC ACID COMPLEX 



inhibition of E. coli and 5. aureus caused by sulphonamides, although 

 J. O. Lampen and M. J. Jones ^^ had found that low levels of folic 

 acid did not. With L. arabinosus the antagonism of sulphonamide 

 inhibition by folic acid was non-competitive. This kind of synergism 

 between the pteridines and sulphonamides is not unexpected as they 

 are competing with two different parts of the folic acid molecule. The 

 sulphonamides interfere with the functioning of an enzyme that syn- 

 thesises folic acid, whilst the inhibitory pteridines presumably compete 

 with the formation of an enzyme of which folic acid is the prosthetic 

 group. Substitution of the amino groups in 2 : 4-diamino-6 : 7-di- 

 phenylpteridine by acetyl or methyl groups or the introduction of 

 amino, acetylamino or hydroxyl groups into the phenyl nuclei con- 

 siderably increased the inhibitory action on 5. faecalis.^^^ 



Several of the pteridine derivatives tested by Daniel et al.^ (page 

 514) inhibited growth and haemoglobin formation in chicks, notably 

 2-amino-4-hydroxy-6 : 7-dimethylpteridine and 2-amino-4-hydroxy- 

 6 : 7-diphenylpteridine. Several other compounds had no effect on 

 growth but reduced the haemoglobin, and one compound, 2-amino-4- 

 hydroxy-6(or 7)-hydroxy-7(or 6)-methylpteridine, increased the weight 

 but depressed haemoglobin formation. The inhibitory compounds 

 interfered with folic acid metabolism, for reduced levels of the vitamin 

 were found in the liver and blood after administration of the substance. 



The most important growth inhibitors related to pteroylglutamic 

 acid, however, are either homologues or compounds derived from 

 pteroylglutamic acid by the replacement of one or more substituent 

 by some other group. To facilitate the description of these com- 

 pounds, the atoms comprising the pteroyl radicle have been numbered 

 as follows : 



H,N\^N^^K, 



U CH,.NHf ^CO 



e 9 10 -— =/ 



4| 



OH 



It has also become customary to describe the compound obtained 

 by replacing for example the 4-hydroxy group by a 4-amino group as 

 4-aminopteroylglutamic acid, an inaccuracy that can only be excused 

 on the grounds that the correct name would be too ciunbersome for 

 general use. 



7-Methylfolic Acid 



One close structural analogue of folic acid with growth-inhibitory 

 properties is 7-methylfolic acid or, to give it its full chemical name, 



51S 



