Discovery and molecular modeling of novel 1-indolyl acetate--5-nitroimidazole targeting tubulin polymerization as antiproliferative agents

Eur J Med Chem. 2014 Oct 6:85:341-51. doi: 10.1016/j.ejmech.2014.07.082. Epub 2014 Jul 30.

Abstract

A series of 18 novel 1-indolyl acetate-5-nitroimidazole 3a-3r were designed, synthesized, and evaluated for their in vitro biological activities as potential tubulin polymerization inhibitors. Among these compounds, 3p displayed strong antitumor activity with IC50 of 2.00, 1.05, 0.87 μM against A549, Hela and U251 respectively, and also showed the most potent PLK1 inhibitory activity with IC50 of 2.4 μM. Molecular docking studies within the colchicine binding site of tubulin were in good agreement with the tubulin polymerization inhibitory data and confirmed the importance of the configuration of the synthesized 1-indolyl acetate-5-nitroimidazolefor potential tubulin polymerization inhibitors.

Keywords: Docking; Indolyl acetate; Nitroimidazole; Tubulin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Drug Design*
  • Humans
  • Molecular Docking Simulation*
  • Nitroimidazoles / chemical synthesis
  • Nitroimidazoles / chemistry*
  • Nitroimidazoles / metabolism
  • Nitroimidazoles / pharmacology*
  • Protein Multimerization / drug effects*
  • Protein Structure, Quaternary
  • Quantitative Structure-Activity Relationship
  • Tubulin / chemistry*
  • Tubulin / metabolism
  • Tubulin Modulators / chemical synthesis
  • Tubulin Modulators / chemistry
  • Tubulin Modulators / metabolism
  • Tubulin Modulators / pharmacology

Substances

  • Nitroimidazoles
  • Tubulin
  • Tubulin Modulators
  • 4-nitroimidazole