Design, synthesis, biochemical, and biological evaluation of nitrogen-containing trifluoro structural modifications of combretastatin A-4

Bioorg Med Chem Lett. 2008 Sep 15;18(18):5146-9. doi: 10.1016/j.bmcl.2008.07.070. Epub 2008 Jul 24.

Abstract

A new trifluorinated amino-combretastatin analogue, (Z)-2-(4'-methoxy-3'-aminophenyl)-1-(3,4,5-trifluorophenyl)ethene, prepared by chemical synthesis, was found to be a potent inhibitor of tubulin assembly (IC(50)=2.9 microM), and cytotoxic against selected human cancer cell lines. This new lead compound is among the most active from a group of related structural modifications.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Antineoplastic Agents, Phytogenic / chemical synthesis*
  • Antineoplastic Agents, Phytogenic / chemistry
  • Antineoplastic Agents, Phytogenic / pharmacology*
  • Bibenzyls / chemical synthesis*
  • Bibenzyls / chemistry
  • Bibenzyls / pharmacology*
  • Combinatorial Chemistry Techniques
  • Drug Design*
  • Drug Screening Assays, Antitumor
  • Humans
  • Hydrocarbons, Fluorinated / chemical synthesis*
  • Hydrocarbons, Fluorinated / chemistry
  • Hydrocarbons, Fluorinated / pharmacology*
  • Inhibitory Concentration 50
  • Molecular Structure
  • Stereoisomerism
  • Stilbenes / chemistry*
  • Stilbenes / pharmacology*
  • Structure-Activity Relationship
  • Tubulin / metabolism*
  • Tubulin Modulators / pharmacology*

Substances

  • (Z)-2-(4'-methoxy-3'-aminophenyl)-1-(3,4,5-trifluorophenyl)ethene
  • Antineoplastic Agents, Phytogenic
  • Bibenzyls
  • Hydrocarbons, Fluorinated
  • Stilbenes
  • Tubulin
  • Tubulin Modulators
  • fosbretabulin