Organometallic-Tamoxifen Hybrids: A Chronology of the Search for New Selective Estrogen Receptor Modulator

Abstract

Breast cancer account for a quarter of all cancer cases among women. Tamoxifen, the first line charge for breast cancer is a selective estrogen receptor modulator with good recognition ability and cytotoxic effect for breast cancer cells. Prolonged administration of the drug however leads to resistance and development of a secondary tumour. Currently, a modification of tamoxifen with organometallic species such as metallocene (ferrocene and ruthenocene) and substituted metal carbonyls being studied promises to cause irreversible damage to breast cancer cell lines at tolerable doses. In this review we take an overview of such organometallic hybrids that reportedly equipped with appropriate recognition ability, good antiproliferative character and structure-activity potentials that enhances their anticancer activity. Their synthetic pathways are not cumbersome. We also report that the approach is similarly exploring the conjugation of organometallic moieties to organic compounds of promising cytotoxicity other than tamoxifen. Previously screened organic anticancer or modulating agents such as podophyllotoxin and stilbene have also been conjugated to organometallics and evaluated for their actions against breast cancer. The issues of lipophilicity, development of carrier vessels such as cyclodextrin, and the mechanism of action of these drug candidates are all addressed. The review takes a sequential overview of the emergence and efforts made in the search for new organometallic selective estrogen receptor modulators. Keywords: ferrocifen, hydroxyferrocifen, breast cancer, organometallic hybrid, bioorganometallic.