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

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.