Chemical and Biological Studies on 1,2 -Dihydro- s -triazines. IV. Activity in Pteroylglutamic Acid- Streptococcus faecaelis No. 8043 Systems

Abstract

Summary

A series of 71 1,2-dihydro-s-tri-azines have been studied in Streptococcus faecalis No. 8 043-pteroylglutamic acid assay systems. The active derivatives exhibit noncompetitive inhibition over a wide range of concentrations of PGA and differ from 4-aminopteroylglutamic acid in that inhibition is not relieved by adenine or guanine and is irreversible with pteroylglutamic acid. Differences in microbiological activity could be correlated with certain variations in structure and substitution in the molecule with the series. Maximum activity is obtained with 2,2-dimethyl substitution in the triazine ring together with para-and meta-halogen sub-stituents in the phenyl ring. The inhibitory effect of these compounds on Streptococcus faecalis No. 8043 is reversed by appropriate concentrations of dihydropteroylglutamic acid, N¹⁰-formylpteroylglutamic acid, synthetic and natural citrovorum factor and thymine, suggesting that these compounds interfere with the conversion of pteroylglutamic acid to citrovorum factor.