The purpose of this study was to establish the efficacy and mode of ac
tion of peptide boron derivatives as antineoplastic agents and to eval
uate their safety in vivo. Boron-containing phenylalanine and tyrosine
methyl esters were found to be potent cytotoxic agents in a number of
murine and human cancer cell lines. DNA, RNA and protein syntheses we
re inhibited by selected agents, e.g. [(trimethylamine boryl)carbonyl]
-phenylalanine-acetyl ester (9) and N-acetyl-p-boron-phenyl-alanyl-phe
nlalanine-methyl ester (10), in L1210lymphoid leukemia cells. IMP dehy
drogenase, OMP decarboxylase, m-RNA, t-RNA, r-RNA polymerase and ribon
ucleoside reductase activities were inhibited. d(CTP) levels were redu
ced. DNA strand scission occurred after 24 hr incubation. Acute toxici
ty studies in mice demonstrated that the key derivative was safe at th
erapeutic levels with no effects on histology of major organs, hematop
oietic parameters and clinical values.