1-(2-((Z)-6-(2-(Trifluoromethyl)phenyl)hexa-3-en-1,5-diynyl)phenyl)piperidin-2-one as a new potent apoptosis agent

Bioorg Med Chem. 2009 Nov 1;17(21):7412-7. doi: 10.1016/j.bmc.2009.09.042. Epub 2009 Sep 25.

Abstract

Compounds 4a-f, 5a-f and 6-9, showed significant growth inhibition activity against human tumor cell lines. Of these compounds, 1-(2-((Z)-6-(2-(trifluoromethyl)phenyl)hexa-3-en-1,5-diynyl)phenyl)piperidin-2-one (8) displayed the most potent growth inhibition activity. Compound 8 also arrested cancer cells in G2/M phase and induced apoptosis via activation of caspase-3 and -9. According to western-blotting analysis, compound 8 can up-regulate Bax, down-regulate Bcl-2 and XIAP, as well as promote cytochrome c release.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / chemical synthesis
  • Antineoplastic Agents / chemistry*
  • Antineoplastic Agents / pharmacology
  • Apoptosis*
  • Caspase 3 / metabolism
  • Cell Division
  • Cell Line, Tumor
  • Cytochromes c / metabolism
  • Drug Screening Assays, Antitumor
  • G2 Phase
  • HeLa Cells
  • Humans
  • Piperidones / chemical synthesis
  • Piperidones / chemistry*
  • Piperidones / pharmacology
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • Tubulin Modulators / chemical synthesis
  • Tubulin Modulators / chemistry*
  • Tubulin Modulators / pharmacology
  • bcl-2-Associated X Protein / metabolism

Substances

  • 1-(2-((Z)-6-(2-(trifluoromethyl)phenyl)hexa-3-en-1,5-diynyl)phenyl)piperidin-2-one
  • Antineoplastic Agents
  • Piperidones
  • Proto-Oncogene Proteins c-bcl-2
  • Tubulin Modulators
  • bcl-2-Associated X Protein
  • Cytochromes c
  • Caspase 3