THE FOLIC ACID GROUP 593 



faecalis R, which is prevented by folic acid. 151 Quinoxaline derivatives 

 more closely related to folic acid are considerably more effective than the 

 parent compound; 125 however, the compounds with modified ring struc- 

 tures in place of the pteridine ring of folic acid have not as yet been 

 found to be particularly effective as inhibitory analogues of folic acid 

 (Table 22). 



N[N '-{2- Amino- 4- hydroxy -6 -pteridylmethyl) -p-aminobenzenesulfo- 

 nyl]-h-glutamic acid has recently been synthesized, but no biological data 

 were reported. 154 



A number of analogues of folic acid including N-(2-amino-4-hy- 

 droxy-6-pteridylmethyl) -p-aminophenol, N- (2-amino-4-hydroxy-6-pter- 

 idylmethyl) -p-aminohippuric acid, N- (2-amino-4-hydroxy-6-pteridyl- 

 methyl) -4-amino-2-chlorobenzoic acid, 2-hydroxy-2-desaminopteroic 

 acid, 2-hydroxy-2-desaminofolic acid, N-(2-amino-4-hydroxy-6-pteridyl- 

 methyl) -p-aminobenzenesulfonic acid, N- [N- (4- (6-aminoquinazoline) ) 

 p-aminobenzoyl] glutamic acid, N- [N- (4-quinazoline) -p-aminobenzoyl] - 

 glutamic acid, N- (4-aminoquinazoline) -p-aminobenzenesulfonamide, 

 N- [N- (4- (6-nitroquinazoline) ) -p-aminobenzoyl] glutamic acid, N[N- (4- 

 (6-chloroquinazoline) ) -p-aminobenzoyl] glutamic acid, N- [4- (6-chloro- 

 quinazoline) ] -p-aminobenzoic acid, N-(2,4-dihydroxy-6-pteridylmethyl)- 

 p-aminobenzenesulfonic acid, and N-[N-(2,4-dihydroxy-#-methyl-6-pter- 

 idylmethyl)-p-aminobenzoyl] glutamic acid have been prepared, and 

 tested for their effects on the blood pressure of the dog, inhibitory effects 

 on 3,4-dihydroxyphenylalanine decarboxylase, and their inhibitory action 

 on Streptococcus faecalis R. 126 



Previous observations indicated that L-.T-methylfolic acid inhibited to 

 some extent the action of the decarboxylase of 3,4-dihydroxyphenyl- 

 alanine 155 and lowered the blood pressure of the dog. 156 Many of the 

 above compounds, as well as other related inhibitory analogues at con- 

 centrations of 30 to 300 y per cc, show some inhibitory action on the 

 decarboxylase enzyme. 130, 157 The inhibition is reported to be prevented 

 by folic acid in extremely high concentrations, ten to a hundred times the 

 concentration of the inhibitors. Also, some of these analogues affect the 

 blood pressure of the dog. These effects are reported to be nullified by the 

 injection of 250 mg of folic acid per kg of body weight. The pteroic acid 

 analogues are more effective than the folic acid analogues for the hypo- 

 tensive effect. 126 



The Effect of Compounds Related to Folic Acid on Cancer 



An extensive study of B vitamins in normal and cancer tissue has indi- 

 cated that folic acid is relatively the most abundant of the vitamins in 

 cancer tissue. Since there is similarity in the content of the B vitamins 



