Design, synthesis and biological evaluation of (E)-3-(3,4-dihydroxyphenyl)acrylylpiperazine derivatives as a new class of tubulin polymerization inhibitors

Bioorg Med Chem. 2014 Aug 1;22(15):4285-92. doi: 10.1016/j.bmc.2014.05.029. Epub 2014 May 21.

Abstract

A series of novel (E)-3-(3,4-dihydroxyphenyl)acrylylpiperazine derivatives had been synthesized and evaluated their biological activities as potential tubulin polymerization inhibitors. Among these compounds, compound 3q exhibited potent antiproliferative activities against three cancer cell lines in vitro, and antitubulin polymerization activity with IC₅₀ of 0.92 μM, which was superior to that of colchicine (IC₅₀=1.34 μM). Docking simulation was performed to insert compound 3q into the crystal structure of tubulin at colchicine binding site to determine the probable binding model. These results suggested that compound 3q may be a promising antitubulin agent for the potential treatment of cancer.

Keywords: Antiproliferative activity; Antitubulin agent; Dihydroxyphenylacrylylpiperazine; Molecular docking.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Binding Sites
  • Brain / metabolism
  • Cattle
  • Cell Cycle Checkpoints / drug effects
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Colchicine / chemistry
  • Colchicine / metabolism
  • Drug Design*
  • Humans
  • Molecular Docking Simulation
  • Piperazines / chemical synthesis
  • Piperazines / chemistry*
  • Piperazines / pharmacology*
  • Protein Binding
  • Protein Structure, Tertiary
  • Structure-Activity Relationship
  • Tubulin / chemistry*
  • Tubulin / metabolism
  • Tubulin Modulators / chemical synthesis*
  • Tubulin Modulators / chemistry
  • Tubulin Modulators / pharmacology*

Substances

  • Piperazines
  • Tubulin
  • Tubulin Modulators
  • Colchicine