Synthesis and preliminary in vitro biological activity of non-steroidal cytotoxic estrogens designed for the treatment of breast cancer

The development of resistance to endocrine therapy as well as chemotherapy is presently a major problem in the treatment of breast cancer. To minimize this obstacle, new, more selective and potent, chemotherapeutic agents should be designed. One way to improve selectivity is to link a cytotoxic moiety to a molecule possessing an affinity to the estrogen receptor (ER). The latter would be used to direct the cytotoxic portion of the molecule towards the target cells. Our initial approach led us to the synthesis of new triphenylethylene-platinum(II) complexes 1 a-c. The commercially available desoxyanisoin ( 10 ) was efficiently transformed in seven steps into the platinum(II) complexes 1 a-c with an overall yield exceeding 30%. The biological activity of compounds 1 a-c was evaluated in vitro on ER+ and ER− human breast tumor cell lines: MCF-7 and MDA-MD-231.