Inhibition of dihydrofolate reductase. 3. 4,6-Diamino-1,2-dihydro-2,2-dimethyl-1-(2-substituted-phenyl)-s-triazine inhibition of bovine liver and mouse tumor enzymes

Abstract

Inhibition of dihydrofolate reductase from bovine liver and murine L5178YR-C3 tumor cells has been examined for a series of 4,6-diamino-1,2-dihydro-2,2-dimethyl-1-(2-X-phenyl)-s-triazines. For both enzymes all 2-X substituents cause a decrease in inhibitory activity relative to X = H, with the notable exception of X = SH which is 7.4-12 times as active as X = H. Although there is a high correlation between the activities of these compounds vs. these two enzymes, significant deviations from this correlation for three of the triazines (X = CF3, CH2CN, and Cl) suggest that (a) there may exist significant differences in the two enzymes and their interactions with these triazines and (b) exploitation of such differences might allow for the selective inhibition of enzyme from tumor cells.