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

Golara Golbaghi (1) , Mohammad Mehdi Haghdoost (1) , Debbie Yancu (1) , Yossef López de Los Santos (1) , Nicolas Doucet (1) , Shunmoogun A. Patten (1) , J Thomas Sanderson (1) , Annie Castonguay (1)

1 INRS-IAF - Institut Armand Frappier

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(η6-C6H6)(PPh3)(η1-ATZ)Cl]BPh4 (3) was found to be the most stable in cell culture media, to lead to the highest cellular uptake and in vitro 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 3 (12.5 μM) did not lead to noticeable signs of toxicity over 96 h, making it a suitable candidate for further in vivo investigations.

Domaines: Sciences du Vivant [q-bio]

Golara Golbaghi, Mohammad Mehdi Haghdoost, Debbie Yancu, Yossef López de Los Santos, Nicolas Doucet, et al.. Organoruthenium(II) Complexes Bearing an Aromatase Inhibitor: Synthesis, Characterization, in Vitro Biological Activity and in Vivo Toxicity in Zebrafish Embryos. Organometallics, 2019, 38 (3), pp.702-711. ⟨10.1021/acs.organomet.8b00897⟩. ⟨pasteur-02135815⟩