THE FOLIC ACID COMPLEX 



Aminopterin and several related compounds had an inhibitory 

 action on tumour growth (page 523). 



Other potent antagonists of folic acid are obtained by replacing 

 the hydroxyl group in various homologues of pteroylglutamic acid by 

 an amino-group. Thus 4-amino-Ni^-methylpteroylglutamic acid was 

 an antagonist of pteroylglutamic acid for rats, chicks and S. faecalis 

 R ; *^» *^ the inhibitory action on S. faecalis R was reversed by 

 pteroylglutamic acid at all concentrations, but the toxic effect on 

 rats was reversible only over a very narrow range. *^ 



4-Amino-9 : N^^-dimethylpteroylglutamic acid had an antagonist 

 activity of 1560 against 5. faecalis.^'^^ 4-Aminopteroylaspartic acid, 

 made by condensing ^-aminobenzoylaspartic acid with 1:3: 3-tri- 

 bromopropanone-2 and 2:4:5: 6-tetraaminopyrimidine, was a com- 

 petitive antagonist of pteroylglutamic acid in the chick, rat and 

 certain bacteria.*^ j^ produced abnormalities in chick embryos, as 

 did the corresponding alanine and threonine derivatives, but all were 

 less active than 4-aminopteroylglutamic acid.^^ 4-Aminopteroyl 

 derivatives of aminomalonic acid, e-aminocaproic acid, isoleucine, 

 phenylalan;ne, sarcosine, serine, tryptophan and valine have also been 

 prepared. *2 



Xanthopterine and its Derivatives 



Pure xanthopterine and dihydroxanthopterine inhibited the 

 growth of L. helveticus, although impure xanthopterine has been stated 

 to have slight growth-promoting activity.^* According to J. A. 

 Pritchard,^^ xanthopterine failed to cure the symptoms of folic acid 

 deficiency induced in rats by the feeding of succinylsulphathiazole, 

 whereas E. R. Norris and J. J. Majnarich ^^ reported that it produced 

 an immediate and rapid increase in the reticulocytes, red and white 

 blood cells, blood-cell volume and haemoglobin in rats made anaemic 

 by means of sulphathiazole. It also increased the rate of cell pro- 

 liferation of erythrocytes in bone-marrow cultures and increased the 

 numbers of nucleated cells and reticulocytes. A few other substances 

 related to xanthopterine had a similar though less marked effect, but 

 xanthopterine-7-carboxylic acid and 2-amino-4-hydroxy-7-methyl- 

 pteridine were strongly inhibitory ; the effect of the latter w^as antag- 

 onised by xanthopterine.^^ 



Miscellaneous Folic Acid Inhibitors 



A number of substituted pteridine carboxylyl-^-aminobenzoyl- 

 glutamic acids and related compounds were found to inhibit the 

 growth of bacteria by competition with folic acid.*® The most active 

 compound was 2-amino-4:7 - dihydroxypteridine-6-carboxylyl-^-amino- 



522 



