Synthesis and cytotoxic evaluation of combretafurans, potential scaffolds for dual-action antitumoral agents

J Med Chem. 2006 Aug 24;49(17):5372-6. doi: 10.1021/jm060621o.

Abstract

We have synthesized rigid analogues of combretastatin bearing a furan ring in place of the olefinic bridge. These compounds are cytotoxic at nanomolar concentrations in neuroblastoma cells, display a similar structure-activity relationship compared to combretastatin A4, and inhibit tubulin polymerization. We also show that the furan ring can be further functionalized. Thus, it is possible that combretafurans could act as scaffolds for the development of dual-action antitumoral agents.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anisoles / chemical synthesis*
  • Anisoles / chemistry
  • Anisoles / pharmacology*
  • Antineoplastic Agents / chemical synthesis*
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology*
  • Bibenzyls / chemical synthesis*
  • Bibenzyls / chemistry
  • Bibenzyls / pharmacology*
  • Cell Death / drug effects
  • Cell Line, Tumor
  • Drug Screening Assays, Antitumor
  • Furans / chemistry*
  • Humans
  • Molecular Structure
  • Neuroblastoma / drug therapy*
  • Stilbenes / chemical synthesis*
  • Stilbenes / chemistry
  • Stilbenes / pharmacology*
  • Structure-Activity Relationship
  • Tubulin / drug effects

Substances

  • Anisoles
  • Antineoplastic Agents
  • Bibenzyls
  • Furans
  • Stilbenes
  • Tubulin
  • combretastatin
  • fosbretabulin
  • furan