Synthesis and characterisation of estrogenic carriers for cytotoxic Pt(II) fragments: biological activity of the resulting complexes

Org Biomol Chem. 2005 Oct 7;3(19):3531-9. doi: 10.1039/b507716h. Epub 2005 Aug 22.

Abstract

This paper describes the synthesis and the spectroscopic characterisation of cis-dichloro[N-(4-(17alpha-ethynylestradiolyl)-benzyl)-ethylenediamine]platinum(II) and cis-diamino[2-(4-(17alpha-ethynylestradiolyl)-benzoylamino)-malonato]platinum(II). These complexes were synthesised in good yield according to multi-step procedures based on the classical and non-classical Sonogashira coupling reaction, respectively. These compounds retain an acceptable degree of relative binding affinity (RBA) for the alpha form of estrogen receptor. Combined treatment of breast cancer cell lines, namely hormone-sensitive MCF-7 and hormone-insensitive MDA-MB-231 cell lines, indicates that these compounds maintain agonistic activity so that the potential advantage in vehiculation of the cytotoxic moiety by means of the receptor system is counteracted by the proliferative effect of the estrogenic component of the entire molecule, especially at low concentrations.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents, Hormonal / chemical synthesis*
  • Antineoplastic Agents, Hormonal / pharmacology
  • Binding Sites
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / pathology
  • Estradiol / analogs & derivatives*
  • Estradiol / chemical synthesis
  • Estradiol / pharmacology
  • Estrogens / chemistry*
  • Humans
  • Molecular Structure
  • Organoplatinum Compounds / administration & dosage*
  • Organoplatinum Compounds / chemical synthesis
  • Organoplatinum Compounds / chemistry
  • Organoplatinum Compounds / pharmacology
  • Organoplatinum Compounds / therapeutic use
  • Stereoisomerism
  • Tumor Cells, Cultured

Substances

  • Antineoplastic Agents, Hormonal
  • Estrogens
  • Organoplatinum Compounds
  • cis-diamino(2-(4-(17alpha-ethynylestradiolyl)-benzoylamino)-malonato)platinum
  • cis-dichloro(N-(4-(17alpha-ethynylestradiolyl)-benzyl)-ethylenediamine)platinum
  • Estradiol