Stereoselective synthesis and anti-proliferative effects on prostate cancer evaluation of 5-substituted-3,4-diphenylfuran-2-ones

Eur J Med Chem. 2013 Jul:65:323-36. doi: 10.1016/j.ejmech.2013.04.062. Epub 2013 May 14.

Abstract

Series of 5-substituted-3,4-diphenylfuran-2-ones were stereoselectively prepared. Their potential anti-proliferative effects on prostate cancer and some of their cyclooxygenases (COXs) inhibitory activities were evaluated. Structure-activity relationship (SAR) data, acquired by substituent modification at the para-position and ortho-position of the C-3 phenyl ring and 5-substituted modification of the central furanone, showed that 3-(2-chloro-phenyl)-4-(4-methanesulfonyl-phenyl)-5-(1-methoxy-ethyl)-5H-furan-2-one (13p) was the most potent compound and could effectively reduce the proliferation of prostate cancer cells (PC3 cell IC50 = 20 μM; PC3 PCDNA cell IC50 = 5 μM; PC3 SKP2 cell IC50 = 5 μM; DU145 cell IC50 = 25 μM). The cell cycle analysis for 13p in DU145 indicated that 13p may induce G1 phase arrest.

Keywords: 5-Substituted-3,4-diphenylfuran-2-one; Anti-proliferative; Cell cycle arrest; Prostate cancer; Rofecoxib.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / chemical synthesis
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology*
  • Apoptosis / drug effects
  • Cell Proliferation / drug effects
  • Cyclooxygenase 1 / metabolism
  • Cyclooxygenase 2 / metabolism
  • Cyclooxygenase Inhibitors / chemical synthesis
  • Cyclooxygenase Inhibitors / chemistry
  • Cyclooxygenase Inhibitors / pharmacology*
  • Dose-Response Relationship, Drug
  • Drug Screening Assays, Antitumor
  • Furans / chemical synthesis
  • Furans / chemistry
  • Furans / pharmacology*
  • Humans
  • Male
  • Molecular Structure
  • Prostatic Neoplasms / drug therapy*
  • Prostatic Neoplasms / pathology
  • Stereoisomerism
  • Structure-Activity Relationship
  • Tumor Cells, Cultured

Substances

  • 3,4-diphenylfuran-2-one
  • Antineoplastic Agents
  • Cyclooxygenase Inhibitors
  • Furans
  • Cyclooxygenase 1
  • Cyclooxygenase 2