Haghdoost, Mohammad Mehdi; Golbaghi, Golara; Létourneau, Myriam; Patten, Shunmoogum A. et Castonguay, Annie 
ORCID: https://orcid.org/0000-0001-5705-6353
(2017).
Lipophilicity-antiproliferative activity relationship study leads to the preparation of a ruthenium(II) arene complex with considerable in vitro cytotoxicity against cancer cells and a lower in vivo toxicity in zebrafish embryos than clinically approved cis-platin
European Journal of Medicinal Chemistry
, vol. 132
.
pp. 282-293.
DOI: 10.1016/j.ejmech.2017.03.029.
Résumé
Ru(II)-arene complexes are attracting increasing attention due to their considerable antitumoral activity. However, it is difficult to clearly establish a direct relationship between their structure and antiproliferative activity, as substantial structural changes might not only affect their anticancer activity but also tightly control their activation site(s) and/or their biological target(s). Herein, we describe the synthesis and characterization of four ruthenium(II) arene complexes bearing bidentate N,O-donor Schiff-base ligands ([Ru(η6-benzene)(N-O)Cl]) that display a significantly distinct antiproliferative activity against cancer cells, despite their close structural similarity. Furthermore, we suggest there is a link between their respective antiproliferative activity and their lipophilicity, as the latter affects their ability to accumulate into cancer cells. This lipophilicity-cytotoxicity relationship was exploited to design another structurally related ruthenium complex with a much higher antiproliferative activity (IC50 > 25.0 μM) against three different human cancer cell lines. Whereas this complex shows a slightly lower activity than that of clinically approved cis-platin against the same human cancer cell lines, it displays a lower toxicity in zebrafish (Danio rerio) embryos at concentrations up to 20 μM.
| Type de document: | Article |
|---|---|
| Mots-clés libres: | Antiproliferative activity; Cancer; In vivo toxicity; Lipophilicity; Ruthenium complexes; Zebrafish |
| Centre: | Centre INRS-Institut Armand Frappier |
| Date de dépôt: | 29 juin 2017 05:07 |
| Dernière modification: | 21 févr. 2022 17:10 |
| URI: | https://espace.inrs.ca/id/eprint/5370 |
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