Microwave-assisted synthesis and biological evaluation of 3,4-diaryl maleic anhydride/N-substituted maleimide derivatives as combretastatin A-4 analogues

Bioorg Med Chem Lett. 2015 Feb 1;25(3):631-4. doi: 10.1016/j.bmcl.2014.12.004. Epub 2014 Dec 8.

Abstract

A series of new CA-4 analogues bearing maleic anhydride/N-substituted maleimide moiety were synthesized via a microwave-assisted process. They were evaluated for the anti-proliferative activities against three tumor cell lines (SGC-7901, HT-1080 and KB). Most compounds showed moderate potencies in micromolar range, with the most promising analogue 6f showing active at submicromolar concentration against HT-1080 cancer cells which was selected to investigate the antitumor mechanisms. In addition, molecular docking studies within the colchicine binding site of tubulin were also in good agreement with the tubulin polymerization inhibitory data and provided a basis for further structure-guided design of novel CA-4 analogues.

Keywords: Anti-proliferative activity; Combretastatin A-4; Maleic anhydride; N-Substituted maleimide; Tubulin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bibenzyls / chemical synthesis
  • Bibenzyls / chemistry*
  • Bibenzyls / toxicity
  • Binding Sites
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Colchicine / chemistry
  • Colchicine / metabolism
  • Drug Design
  • Humans
  • Maleic Anhydrides / chemistry*
  • Maleimides / chemical synthesis
  • Maleimides / chemistry*
  • Maleimides / toxicity
  • Microwaves*
  • Molecular Docking Simulation
  • Protein Structure, Tertiary
  • Structure-Activity Relationship
  • Tubulin / chemistry
  • Tubulin / metabolism
  • Tubulin Modulators / chemical synthesis*
  • Tubulin Modulators / chemistry
  • Tubulin Modulators / toxicity

Substances

  • Bibenzyls
  • Maleic Anhydrides
  • Maleimides
  • Tubulin
  • Tubulin Modulators
  • maleimide
  • combretastatin
  • Colchicine