Creation of anthracycline prodrug

Although anthracycline antibiotics are widely used in the treatment of cancer, their use is limited due to severe side-effects, including irreversible cardiotoxicity and multi-drug resistance of tumor cells. One of the promising approaches towards “ideal” anthracycline is the creation of anthracycline-based prodrugs, i.e. compounds that are less active than the parent drug (or inactive) and are converted in its active form through a metabolic process. The main goal of the development of anthracycline prodrugs is to increase the selectivity of the drug (doxorubicin or daunorubicin) towards tumor cells with simultaneous decrease in toxicity to normal cells. With this aim different types of anthracycline prodrugs were designed targeting such specific characteristics of tumor cells as lower pH and oxygenation level in comparison with normal cells, higher content of different enzymes etc. Also two-stage “enzyme-prodrug” strategies which include the selective introduction of the enzyme into the tumor cells on the first step and administration of the prodrug which is the substrate for this enzyme on the second step are developed. These strategies are classified depending on the method of “introduction” of the enzyme into tumor cells: antibody-directed enzyme prodrug therapy (ADEPT), virus-directed enzyme prodrug therapy (VDEPT) and genedirected enzyme prodrug therapy (GDEPT). The review covers recent achievements in the field of creation of different types of anthracycline prodrugs

anthracycline antibiotics, doxorubicin, daunorubicin, prodrug, antiproliferative activity, antitumor activity.

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