Exploring the Anticancer Potential of Diiron Bis-cyclopentadienyl Complexes with Bridging Hydrocarbyl Ligands: Behavior in Aqueous Media and <i>In Vitro</i> Cytotoxicity
Gabriele Agonigi, Lorenzo Biancalana, Maria Giovanna Lupo, Monica Montopoli, Nicola Ferri, Stefano Zacchini, Francesca Binacchi, Tarita Biver, Beatrice Campanella, Guido Pampaloni, Valerio Zanotti, Fabio Marchetti
Abstract
A series of diiron complexes based on the [Fe2Cp2(CO)x] skeleton (Cp = η5-C5H5, x = 2, 3; η4-C5H5Ph in place of one Cp in one case) and containing different bridging hydrocarbyl ligands (aminocarbyne, thiocarbyne, allenyl) were preliminarily investigated for their anticancer potential. The water solubility, stability in water and in the presence of a cell culture medium, and octanol/water partition coefficient were evaluated by spectroscopic techniques. The cytotoxicity was assessed in vitro toward the human ovarian carcinoma cell line A2780, the human triple negative breast cancer cell line MDA-MB-231, and the human vascular smooth muscle cell line SMC. Some aminocarbyne complexes exhibited a potent cytotoxicity, with IC50 values in the low micromolar/nanomolar range, and a strong selectivity for the A2780 cells in comparison to the SMC cell line. Several experiments were carried out in order to give insight into the mode of action of selected compounds, including an assessment of catalytic NADH oxidation and ROS production and studies of binding with DNA and with a model protein.