Enantioselective Synthesis of Planar Chiral Ferrocifens that Show Chiral Discrimination in Antiproliferative Activity on Breast Cancer Cells

Chembiochem. 2020 Oct 15;21(20):2974-2981. doi: 10.1002/cbic.202000311. Epub 2020 Jun 30.

Abstract

The design and first enantioselective synthesis of a series of chiral ferrocifens and ferrociphenols was realised by enantioselective palladium-catalysed intramolecular direct C-H bond activation followed by McMurry coupling. Biological evaluation revealed moderate anticancer activities on breast cancer cells and evidence of chiral discrimination between enantiomers. Treatment of the novel ferrocifens with Ag2 O revealed that these systems are unable to form a neutral quinone methide, yet still demonstrate marked antiproliferative properties against both the hormone-dependent MCF-7 and hormone-independent MDA-MB-231 cell lines. This bioactivity arises from two mechanisms: Fenton-type chemistry and the anti-estrogenic activity associated with the tamoxifen-like structure.

Keywords: anti-tumor agents; bio-organometallics; chirality; enantioselective synthesis; ferrocifen.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / chemical synthesis
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology*
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / pathology
  • Catalysis
  • Cell Proliferation / drug effects
  • Dose-Response Relationship, Drug
  • Drug Screening Assays, Antitumor
  • Female
  • Ferrous Compounds / chemical synthesis
  • Ferrous Compounds / chemistry
  • Ferrous Compounds / pharmacology*
  • Humans
  • Molecular Structure
  • Palladium / chemistry
  • Stereoisomerism
  • Structure-Activity Relationship
  • Tumor Cells, Cultured

Substances

  • Antineoplastic Agents
  • Ferrous Compounds
  • ferrocifen
  • ferrociphenol
  • Palladium