THE EFFECTS OF BORON-CONTAINING PEPTIDES ON L1210 LYMPHOID LEUKEMIA METABOLISM

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.