Development of constrained tamoxifen mimics and their antiproliferative properties against breast cancer cells

Bioorg Med Chem Lett. 2015 Feb 1;25(3):680-4. doi: 10.1016/j.bmcl.2014.11.077. Epub 2014 Dec 5.

Abstract

An efficient synthesis of a new series of tamoxifen mimics is described by employing iodine catalyzed ipsocyclization strategy followed by Suzuki coupling. A molecular docking studies of the synthesized compounds 11a-n and 12 in estrogen receptor (ER-α) showed that the scaffolds are fitting well in the groove, thereby suggesting them as promising antiproliferative agents for estrogen dependent breast cancer lines. All compounds were tested in vitro against breast cancer cell lines-ER positive, MCF-7; ER negative, MDA-MB-231; and control mammary epithelial cells, MEpiC. The biological results showed that most of the compounds are active against MCF-7 with IC50 values less than 6.5μM which corroborate the results of molecular docking studies.

Keywords: Breast cancer; Ipsocyclization; Molecular docking; SERMs; Tamoxifen.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Binding Sites
  • Boronic Acids / chemical synthesis
  • Boronic Acids / chemistry*
  • Boronic Acids / toxicity
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / pathology
  • Catalysis
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Coordination Complexes / chemistry
  • Estrogen Receptor alpha / chemistry
  • Estrogen Receptor alpha / metabolism
  • Female
  • Humans
  • MCF-7 Cells
  • Molecular Docking Simulation
  • Palladium / chemistry
  • Protein Structure, Tertiary
  • Tamoxifen / analogs & derivatives*
  • Tamoxifen / chemical synthesis
  • Tamoxifen / toxicity

Substances

  • Boronic Acids
  • Coordination Complexes
  • Estrogen Receptor alpha
  • Tamoxifen
  • Palladium