Discovery of azaisoerianin derivatives as potential antitumors agents

Eur J Med Chem. 2014 May 6:78:178-89. doi: 10.1016/j.ejmech.2014.03.032. Epub 2014 Mar 13.

Abstract

A series of N-methyl-diarylamines 2 was designed and synthesized as a novel class of CA-4 and isoCA-4 analogues. Compounds 2b and 2m showed excellent antiproliferative activity with mean GI50 values at a nanomolar level in a diverse set of human cancer cells. These compounds also inhibited tubulin assembly at a micromolar range, arrested the cellular cycle in the G2/M phase and induced apoptosis at very low concentrations. Preliminary in vitro results revealed that 2b and 2m displayed substantial efficacy as potent antivascular agents. Docking studies indicates that these lead compounds showed a binding mode similar to those observed with isoCA-4 at the colchicine binding site of tubulin.

Keywords: Antimitotic; AzaisoCA-4; Combretastatin A-4; Cytotoxicity; IsoCA-4; Isoerianin; Tubulin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / chemical synthesis
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology*
  • Apoptosis / drug effects
  • Aza Compounds / chemical synthesis
  • Aza Compounds / chemistry
  • Aza Compounds / pharmacology*
  • Bibenzyls / chemical synthesis
  • Bibenzyls / chemistry
  • Bibenzyls / pharmacology*
  • Binding Sites / drug effects
  • Cell Cycle / drug effects
  • Cell Line
  • Cell Proliferation / drug effects
  • Dose-Response Relationship, Drug
  • Drug Discovery*
  • Drug Screening Assays, Antitumor
  • HCT116 Cells
  • Human Umbilical Vein Endothelial Cells / drug effects*
  • Humans
  • K562 Cells
  • Models, Molecular
  • Molecular Structure
  • Phenol
  • Sheep
  • Structure-Activity Relationship
  • Tubulin / metabolism

Substances

  • Antineoplastic Agents
  • Aza Compounds
  • Bibenzyls
  • Erianin
  • Tubulin
  • Phenol