Novel imidazole-based combretastatin A-4 analogues: evaluation of their in vitro antitumor activity and molecular modeling study of their binding to the colchicine site of tubulin

Bioorg Med Chem Lett. 2006 Nov 15;16(22):5757-62. doi: 10.1016/j.bmcl.2006.08.087. Epub 2006 Sep 6.

Abstract

The in vitro antitumor activity of novel combretastatin-like 1,5- and 1,2-diaryl-1H-imidazoles was evaluated against the NCI 60 human tumor cell lines panel. Compounds 2d and 2g proved to be more cytotoxic than CA-4 in tests involving their evaluation over a 10(-4)-10(-8) range. Docking experiments showed a good correlation between the MG_MID Log GI(50) values of all these compounds and their calculated interaction energies with the colchicine binding site of alphabeta-tubulin.

Publication types

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

MeSH terms

  • Antineoplastic Agents / pharmacology*
  • Antineoplastic Agents / toxicity
  • Binding Sites
  • Cell Line, Tumor / drug effects
  • Colchicine / pharmacology
  • Humans
  • Imidazoles / chemistry*
  • Imidazoles / pharmacology
  • Stilbenes / chemistry
  • Stilbenes / pharmacology*
  • Tubulin / drug effects*
  • Tubulin / metabolism

Substances

  • Antineoplastic Agents
  • Imidazoles
  • Stilbenes
  • Tubulin
  • imidazole
  • fosbretabulin
  • Colchicine