Elaboration of thorough simplified vinca alkaloids as antimitotic agents based on pharmacophore similarity

Eur J Med Chem. 2013 Jul;65:158-67. doi: 10.1016/j.ejmech.2013.04.057. Epub 2013 May 3.


Thorough simplification of vinca alkaloids based on pharmacophore similarity has been conducted. A concise process for the syntheses of target compounds was successfully developed with yields from poor to excellent (19-98%). Cell growth inhibitory activities of these synthesized compounds were evaluated in five cancer cell lines including MCF-7, MDA-MB-231, HepG2, HepG2/ADM and K562. Almost all compounds exhibited moderate antitumor activity with optimal IC50 value of 0.89 ± 0.07 μM in MCF-7 cells. Investigation of structure-activity relationship (SAR) indicates that electron-withdraw substituents on the ring contribute to the enhancement of the antitumor activities. The simplified vinca alkaloids are confirmed as antimitotic agents, which inhibit the polymerization of tubulin just like vinblastine.

Keywords: Anticancer; Antimitotic agent; Pharmacophore similarity; Vinca alkaloid.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antimitotic Agents / chemical synthesis
  • Antimitotic Agents / chemistry
  • Antimitotic Agents / pharmacology*
  • Cell Cycle / drug effects
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Crystallography, X-Ray
  • Dose-Response Relationship, Drug
  • Drug Screening Assays, Antitumor
  • Hep G2 Cells
  • Humans
  • K562 Cells
  • MCF-7 Cells
  • Models, Molecular
  • Molecular Structure
  • Structure-Activity Relationship
  • Vinca Alkaloids / chemical synthesis
  • Vinca Alkaloids / chemistry
  • Vinca Alkaloids / pharmacology*


  • Antimitotic Agents
  • Vinca Alkaloids