Organoruthenium(II) Complexes Bearing an Aromatase Inhibitor: Synthesis, Characterization, <i>in Vitro</i> Biological Activity and <i>in Vivo</i> Toxicity in Zebrafish Embryos

Third-generation aromatase inhibitors such as anastrozole (ATZ) and letrozole (LTZ) are widely used to treat estrogen receptor-positive ER+ breast cancers in postmenopausal women. Investigating their ability to coordinate metals could lead to the emergence of a new category of anticancer drug candidates with a broader spectrum of pharmacological activities. In this study, a series of ruthenium (II) arene complexes bearing the aromatase inhibitor anastrozole was synthesized and characterized. Among these complexes, [Ru(<i>η</i> ⁶ <i>-</i>C₆H₆)(PPh₃)(<i>η</i> ¹ <i>-</i>ATZ)Cl]BPh₄ (<b>3</b>) was found to be the most stable in cell culture media, to lead to the highest cellular uptake and <i>in vitro</i> cytotoxicity in two ER+ human breast cancer cell lines (MCF7 and T47D), and to induce a decrease in aromatase activity in H295R cells. Exposure of zebrafish embryos to complex <b>3</b> (12.5 μM) did not lead to noticeable signs of toxicity over 96 h, making it a suitable candidate for further <i>in vivo</i> investigations.