Functionalized Ferrocenes as Estrogen\'s Pendant Group: Synthesis, Characterization and Biomedical Application
Breast cancer represents about 50% of the cancer incidence rate in women's population, being the Estrogen Receptor Positive (ER+) the most common in this group. In fact, the over-expression of the alpha estrogen receptor (ER?) in hormone dependent cancer is responsible for the abnormally increase of cell proliferation rate. Conventional metal-based therapeutics drugs, such as cisplatin and derivatives, are still used to inhibit this abnormal cellular proliferation rate. However, cisplatin-based drugs are highly cytotoxic, triggering a series of side effects that become detrimental to the body, due to their lack of selectivity between healthy and cancerous tissue. In 1984, Köpf-Maier, and his co-workers first reported the anticancer properties of ferrocene. This organometallic compound leads to the formation of radical oxygen species that cause oxidative damage to DNA, inducing cell apoptosis. The incorporation of ferrocene into hydroxytamoxifen frame was successfully performed showing impressive cytotoxic activity results. Hydroxytamoxifen shows only activity on hormone dependent MCF-7 breast cancer, while hydroxyferroxicen show activity in both, hormone dependent and independent breast cancer cell lines. In order to develop a novel metal-based therapeutic drug with a high selective index over the cancer tissue, estrogen hormones have been functionalized with ferrocene as pendant group. In this work, we present a series of synthesized ferrocene complexes with its characterization by X-Ray crystallography, in vitro cytotoxic studies on hormone-dependent MCF-7 cell line and docking studies on the ER?.