PUBLICATION
Organoruthenium(II) Complexes Bearing an Aromatase Inhibitor: Synthesis, Characterization, in Vitro Biological Activity and in Vivo Toxicity in Zebrafish Embryos
- Authors
- Golbaghi, G., Haghdoost, M.M., Yancu, D., Santos, Y.L.L., Doucet, N., Patten, S.A., Sanderson, J.T., Castonguay, A.
- ID
- ZDB-PUB-191126-5
- Date
- 2019
- Source
- Organometallics 38: 702-711 (Journal)
- Registered Authors
- Patten, Shumoogum
- Keywords
- none
- MeSH Terms
- none
- PubMed
- 31762529 Full text @ Organometallics
Citation
Golbaghi, G., Haghdoost, M.M., Yancu, D., Santos, Y.L.L., Doucet, N., Patten, S.A., Sanderson, J.T., Castonguay, A. (2019) Organoruthenium(II) Complexes Bearing an Aromatase Inhibitor: Synthesis, Characterization, in Vitro Biological Activity and in Vivo Toxicity in Zebrafish Embryos. Organometallics. 38:702-711.
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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Human Disease / Model
Sequence Targeting Reagents
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