Synthesis and Preliminary in Vitro Cytotoxic Activity of New Triphenylethylene Dimers

We have synthesized a series of six nonsteroidal homo- and heterobifunctional estrogenic dimers designed for the treatment of breast cancer. They are made of two triphenylethylene moieties linked by an aliphatic chain. The synthesis used six steps, from the known alcohol 5, with an overall yield of more than 60%. This article describes the synthesis of these products and their in vitro biological activity on two human breast cancer cell lines: MCF-7 and MDA-MB-231. The dimers are generally less active than tamoxifen, which presents an IC50 = 16 and 40 μM on MCF-7 and MDA-MB-231 cell lines, respectively. However, the symmetrical dimer bearing six hydroxy functions possesses the best in vitro cytotoxic activity of the series, showing an IC50 = 38 μM on both types of cells. It was observed that the cytotoxicity of the dimers increases with the number of hydroxy groups present on the aromatic rings.