Photoresponsive azo-combretastatin A-4 analogues

Eur J Med Chem. 2018 Jan 1;143:1-7. doi: 10.1016/j.ejmech.2017.11.012. Epub 2017 Nov 10.


Colchicine analogues in which an azo group is incorporated into a molecule containing the key pharmacophore of colchicine, have found particular utility as switchable tubulin binding chemotherapeutics. Combretastatin is a related compound containing a stilbene fragment that shows different bioactivity for the cis and trans isomers. We have performed cell assays on 17 new compounds structurally related to a previously reported azo-analogue of combretastatin. One of these compounds showed enhanced potency against HeLa (IC50 = 0.11 μM) and H157 cells (IC50 = 0.20 μM) for cell studies under 400 nm irradiation and the highest photoactivity (IC50 with irradiation/IC50 in dark = 550). We have performed docking and physicochemical studies of this new compound (7). Kinetic studies in water reveal a longer half-life for the cis isomer of 7 which may be one factor responsible for the better IC50 values in cell assays and the improved photoresponsive behavior.

Keywords: Azobenzene; Colchicine; Combretastatin; Photopharmacology; Tubulin.

MeSH terms

  • Antineoplastic Agents / chemical synthesis
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology*
  • Azo Compounds / chemical synthesis
  • Azo Compounds / chemistry
  • Azo Compounds / pharmacology*
  • Cell Proliferation / drug effects
  • Dose-Response Relationship, Drug
  • Drug Screening Assays, Antitumor
  • Humans
  • Kinetics
  • Ligands
  • Molecular Structure
  • Photochemical Processes
  • Stilbenes / chemical synthesis
  • Stilbenes / chemistry
  • Stilbenes / pharmacology*
  • Structure-Activity Relationship
  • Ultraviolet Rays


  • Antineoplastic Agents
  • Azo Compounds
  • Ligands
  • Stilbenes
  • fosbretabulin