Synthesis and Biological Activity of New Functionalized Epothilones for Prodrug Design and Tumor Targeting

Authors

  • Silvia Anthoine Dietrich
  • Linda Riediker
  • Jürg Gertsch Institute of Biochemistry and Molecular Medicine, University of Bern, Bern
  • Karl-Heinz Altmann Swiss Federal Institute of Technology (ETH) Zürich, Institute of Pharmaceutical Sciences, ETH Hönggerberg, HCI H 405, CH-8093 Zürich

DOI:

https://doi.org/10.2533/chimia.2010.136

Keywords:

Antiproliferative agent, Drug conjugate, Epothilone, Total synthesis, Tumor targeting

Abstract

Epothilones are potent antiproliferative agents, which have served as successful lead structures for anticancer drug discovery. However, their therapeutic efficacy would benefit greatly from an increase in their selectivity for tumor cells, which may be achieved through conjugation with a tumor-targeting moiety. Three novel epothilone analogs bearing variously functionalized benzimidazole side chains were synthesized using a strategy based on palladium-mediated coupling and macrolactonization. The synthesis of these compounds is described and their in vitro biological activity is discussed with respect to their interactions with the tubulin/microtubule system and the inhibition of human cancer cell proliferation. The additional functional groups may be used to synthesize conjugates of epothilone derivatives with a variety of tumor-targeting moieties.

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Published

2010-03-31

How to Cite

[1]
S. A. Dietrich, L. Riediker, J. Gertsch, K.-H. Altmann, Chimia 2010, 64, 136, DOI: 10.2533/chimia.2010.136.