2. Academic Validation
  3. Synthesis, hydrolytic activation and cytotoxicity of etoposide prodrugs

Synthesis, hydrolytic activation and cytotoxicity of etoposide prodrugs

  • Bioorg Med Chem Lett. 2002 Feb 25;12(4):557-60. doi: 10.1016/s0960-894x(01)00801-0.
Wolf Wrasidlo 1,  Ulrike Schröder,  Kathrin Bernt,  Nicole Hübener,  Doron Shabat,  Gerhard Gaedicke,  Holger Lode
Affiliations

Affiliation

  • 1 Charité Children's Hospital, Humboldt University, Augustenburger Platz 1, 13353 Berlin, Germany. wrasidlo@charite.de
PMID: 11844671 DOI: 10.1016/s0960-894x(01)00801-0
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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