Improved antitumor activity of basic amino acid and dipeptide derivatives of daunorubicin on EL4 leukemia cells in mice.

Over thirty amino acid and peptide derivatives of the antitumor drug daunorubicin (DM) were tested for their potency to inhibit EL4 leukemia cell growth in mice. The therapeutic effect of the basic amino acids lysine, arginine, ornithine, and 2,4-diaminobutyric acid coupled to the amino group of the DM moiety proved superior to that of the parent drug. The derivatized amino acids and their di- or tripeptides are significantly less toxic than DM, which enabled their administration at much higher doses. Seventy percent to 80% of tumor-bearing C57BL/6 mice were cured by multidose treatment with diaminobutyryl-DM, which was found to be the most efficient derivative.