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. Epub 2015 Mar 7.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / chemical synthesis*
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • HCT116 Cells
  • Humans
  • K562 Cells
  • Tubulin / chemistry
  • Tubulin / metabolism
  • Tubulin Modulators / chemical synthesis
  • Tubulin Modulators / chemistry
  • Tubulin Modulators / pharmacology
  • Vinblastine / analogs & derivatives*
  • Vinblastine / chemical synthesis
  • Vinblastine / chemistry
  • Vinblastine / pharmacology
  • Vinca Alkaloids / chemistry
  • Vinorelbine

Substances

  • Antineoplastic Agents
  • Tubulin
  • Tubulin Modulators
  • Vinca Alkaloids
  • Vinblastine
  • Vinorelbine