Hydrazone, Amide, Carbamate, Macromolecular and Other Prodrugs of Doxorubicin

The term prodrug was first used by Albert [1]. Prodrug can be defined as an agent that is transformed after administration, either by metabolism or by spontaneous chemical breakdown, to form a pharmacologically active drug. The prodrug itself is inactive or less active and is converted to active agent in vivo. Targeted prodrug approach is one of the new trends in the treatment of cancer. A lot of antitumor drugs possess a limited bioavailability due to low chemical stability, limited oral absorption or rapid metabolism [2]. Because of these problems, different prodrug models that can be activated into antitumor drugs have been designed. An improved solubility can facilitate oral absorption, while improving chemical stability of an active drug. An ideal prodrug is designed to increase the bioavailability and to eliminate undesirable side effects of antitumor drug. Prodrugs of antitumor agents are also designed as organ-specific and tumor-specific targeting. An important strategy to achieve local activation of prodrugs is the use of enzyme immunoconjugates. In this approach, which is called antibody-directed enzyme prodrug therapy (ADEPT) [3], an enzyme is conjugated to a tumor-specific antibody. Alternative approaches for the design of ADEPT are gene-directed enzyme prodrug therapy (GDEPT) [4-6] and virus-directed enzyme prodrug therapy (VDEPT) [7].