Synthesis, hydrolytic activation and cytotoxicity of etoposide prodrugs |
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| Authors: | Wrasidlo Wolf Schröder Ulrike Bernt Kathrin Hübener Nicole Shabat Doron Gaedicke Gerhard Lode Holger |
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| Institution: | Charité Children's Hospital, Humboldt University, Augustenburger Platz 1, 13353 Berlin, Germany. wrasidlo@charite.de |
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| Abstract: | Two 4'-propylcarbonoxy derivatives (2,3) of etoposide (1), a topoisomerase II inhibitor, were synthesized and evaluated as potential prodrugs for anticancer therapy. Their activation via hydrolysis mechanisms was determined as a function of pH in buffer solutions, in human serum and in the presence of carboxyl ester hydrolase. Cytotoxicity was determined on various tumor cell lines and compared to the parent compound. On cell lines exhibiting resistance to etoposide we observed an enhanced cytotoxicity of the prodrugs of up to three orders of magnitude. |
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