Amino acid and dipeptide derivatives of daunorubicin. 1. Synthesis, physicochemical properties, and lysosomal digestion.
The synthesis of amino acid and dipeptide derivatives of daunorubicin (DNR) is described. The binding-affinity parameters for DNA of those derivatives were determined by a spectral titration method. The affinity constants of the amino acid and dipeptide derivatives are, respectively, three and ten times lower than that of DNR. The susceptibility of those derivatives toward lysosomal peptidases was studied. It was found that the Leu and the Ala-Leu derivatives are the most rapidly hydrolyzed into DNR. It is concluded that Leu-DNR and Ala-Leu-DNR could act as prodrugs of DNR, which could be activated inside or in the close vicinity of tumor cells which display a high aminopeptidase activity.
D000818:Animals; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D004247:DNA / Q000378:metabolism; D003630:Daunorubicin / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000378:metabolism; D005399:Fishes; D006863:Hydrogen-Ion Concentration; D006868:Hydrolysis; D066298:In Vitro Techniques; D008099:Liver / Q000378:metabolism; D008247:Lysosomes / Q000378:metabolism*; D051381:Rats
D004247:DNA; D003630:Daunorubicin