Sturcture-activity relationship of daunorubicin and its peptide derivatives

The synthesis of potentially specific antitumor peptide derivatives of daunorubicin is presented. The interaction specificites of the drugs with nucleic acids have been examined via stop-flow kinetics as well as the inhibition of DNA template activity. It is found that the biological activity of the daunorubicin derivatives against the mouse P388 tumor is directly proportional to RNA polymerase inhibition and inversely proportional to the rate of dissociation of the DNA complex. It is concluded that the biological efficacy of drugs which act at the replicative and transcriptional level may be estimated by the more rapid in vitro techniques provided that problems of permeability, solubility, stability, etc., in vivo are not encountered.