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 Patten 1 J Thomas Sanderson 1 Annie Castonguay 1
1 INRS-IAF - Institut Armand Frappier
Abstract : 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.
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Submitted on : Tuesday, May 21, 2019 - 3:38:33 PM
Last modification on : Tuesday, May 28, 2019 - 11:05:31 AM

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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, American Chemical Society, 2019, 38 (3), pp.702-711. ⟨10.1021/acs.organomet.8b00897 ⟩. ⟨pasteur-02135815⟩

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