Synthesis of prodrugs of anthracyclines and evaluation of their use in selective chemotherapy
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[S.l. : s.n.]
Number of pages
VIII, 136 p.
Promotores : B. Zwanenburg en J. Scheeren
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Faculty of Science
This thesis is devoted to the synthesis and biological evaluation of prodrugs of anthracycline anti-tumor antibiotics designed for use in selective chemotherapy. The severe side effects caused by conventional cancer chemotherapeutic agents arises from the lack of distinction between tumor and normal cells. Most of the available antitumor drugs are specifically toxic to proliferating cells and, therefore, tumor cells are slightly more sensitive to cytostatic agents compared with normal cells. Nevertheless, therapeutic indices of anticancer drugs are too low resulting in unacceptable damage to healthy tissue upon chemo-treatment. This has stimulated the development of a variety of approaches to improve the effectiveness and tumor cell selectivity of anticancer agents. In this thesis the synthesis of prodrugs which can be used in the Antibody Directed Enzyme Prodrug Therapy (ADEPT) concept for selective cancer treatment is described. A concise biological evaluation of the synthesized prodrugs for the ADEPT concept is given at the end of each chapter.
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