Synthesis, biological evaluation and molecular modeling of 1,2,3-triazole analogs of combretastatin A-1

Bioorg Med Chem. 2012 Jan 1;20(1):234-42. doi: 10.1016/j.bmc.2011.11.010. Epub 2011 Nov 12.

Abstract

The synthesis, cytotoxicity, inhibition of tubulin polymerization data and anti-angiogenetic effects of seven 1,5-disubstituted 1,2,3-triazole analogs and two 1,4-disubstituted 1,2,3-triazole analogs of combretastatin A-1 (1) are reported herein. The biological studies revealed that the 1,5-disubstituted 1,2,3-triazoles 3-methoxy-6-(1-(3,4,5-trimethoxyphenyl)-1H-1,2,3-triazol-5-yl)benzene-1,2-diol (6), 3-methoxy-6-(1-(3,4,5-trimethoxyphenyl)-1H-1,2,3-triazol-5-yl)benzene-1,2-diamine (8) and 5-(2,3-difluoro-4-methoxyphenyl)-1-(3,4,5-trimethoxyphenyl)-1H-1,2,3-triazole (9) were the three most active compounds regarding inhibition of both tubulin polymerization and angiogenesis. Molecular modeling studies revealed that combretastatins 1 and 2 and analogs 5-11 could be successfully docked into the colchicine binding site of α,β-tubulin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiogenesis Inhibitors / chemical synthesis*
  • Angiogenesis Inhibitors / chemistry
  • Angiogenesis Inhibitors / pharmacology
  • Binding Sites
  • Cell Line
  • Humans
  • Models, Molecular*
  • Molecular Dynamics Simulation
  • Polymerization / drug effects
  • Protein Structure, Tertiary
  • Stilbenes / chemistry*
  • Triazoles / chemical synthesis
  • Triazoles / chemistry*
  • Triazoles / pharmacology
  • Tubulin / chemistry
  • Tubulin / metabolism
  • Tubulin Modulators / chemical synthesis*
  • Tubulin Modulators / chemistry
  • Tubulin Modulators / pharmacology

Substances

  • Angiogenesis Inhibitors
  • Stilbenes
  • Triazoles
  • Tubulin
  • Tubulin Modulators
  • combretastatin A-1