A hypothesis on a possible competitive relation between DNA synthesis and protein synthesis.

Summary Twenty-four congeners of folic acid were rated with respect to their relative effectiveness in increasing the survival time of mice with advanced leukemia L1210. The following general structure-activity relationships were observed with these compounds. 1.Appreciable antileukemic activity was found only among the compounds with the 4-amino moiety. 2.Among the 4-amino derivatives of folic acid, antileukemic effectiveness may be increased by certain substitutions including (a) methyl or ethyl substitution in the 10 position, and (b) halogenation in the benzene ring of the p-amino benzoic acid moiety. The most effective of the compounds tested were the 4-amino-10-methyl-3′,5′-dihalogenated derivatives of folic acid. 3.Substitutions for glutamic acid in the 4-amino derivatives of folic acid did not markedly alter their activity.