Synthesis and biological evaluation of C-13' substituted 7'-homo-anhydrovinblastine derivatives

  • Bioorg Med Chem Lett. 2015 Apr 15;25(8):1771-1773. doi: 10.1016/j.bmcl.2015.02.045.
Olga Gherbovet  1 ,  Fabio La Spisa  2 ,  Sylviane Thoret  1 ,  Maria Concepcion Garcia Alvarez  1 ,  Hélène Levaique  1 ,  Jérôme Bignon  1 ,  Fanny Roussi  3
Affiliations
  • 1. Centre de Recherche de Gif, Institut de Chimie des Substances Naturelles, UPR 2301 du CNRS, Avenue de la Terrasse, 91198 Gif-sur-Yvette Cedex, France.
  • 2. Dipartimento di Scienze del Farmaco, Università degli Studi del Piemonte Orientale 'A. Avogadro', Largo Donegani 2, 28100 Novara, Italy.
  • 3. Centre de Recherche de Gif, Institut de Chimie des Substances Naturelles, UPR 2301 du CNRS, Avenue de la Terrasse, 91198 Gif-sur-Yvette Cedex, France. Electronic address: [email protected].
PMID: 25804719 DOI: 10.1016/j.bmcl.2015.02.045
Abstract

Recent publications highlighted that vinca derivatives either functionalized on C-12' or enlarged on cycle C' could be more cytotoxic than vinblastine or vinorelbine, both used in anti-cancer therapy. By combining these two results, nine new 7'-homo-anhydrovinblastine derivatives functionalized on C-13' were elaborated. The synthesis of key intermediates, their one-step transformation into final products in mild conditions and their biological activities are presented.

Keywords
7′-homo-Anhydrovinblastine; Cancer; Cytotoxicity; Tubulin; Vinca alkaloids.