2-(6-aryl-3(Z)-hexen-1,5-diynyl)anilines as a new class of potent antitubulin agents

J Med Chem. 2008 May 8;51(9):2682-8. doi: 10.1021/jm070820n. Epub 2008 Apr 3.

Abstract

Compounds 2a- h and 6 displayed significant GI 50 values of 10(-7)-10(-6) M against various cancer cell lines. Of these compounds, 2-(6-(2-trifluoromethylphenyl))-3(Z)-hexen-1,5-diynyl)aniline (2c) showed the most potent growth inhibition activity. Compound 2c also arrested cancer cells in the G2/M phase and in low concentration reduced a significant percentage of MDA-MB-231/ATCC breast cancer tetraploid cells. In addition to the G2/M block, compound 2c caused microtubule depolymerization and induced apoptosis via activation of the caspase family.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aniline Compounds / chemical synthesis*
  • Aniline Compounds / chemistry
  • Aniline Compounds / pharmacology
  • Biopolymers
  • Cell Cycle / drug effects
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Drug Screening Assays, Antitumor
  • Humans
  • Microtubules / drug effects
  • Microtubules / ultrastructure
  • Stereoisomerism
  • Structure-Activity Relationship
  • Tubulin / chemistry
  • Tubulin Modulators / chemical synthesis*
  • Tubulin Modulators / chemistry
  • Tubulin Modulators / pharmacology

Substances

  • 2-(6-(2-trifluoromethylphenyl))-3-(hexen-1,5-diynyl)aniline
  • Aniline Compounds
  • Biopolymers
  • Tubulin
  • Tubulin Modulators