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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

Haghdoost, Mohammad Mehdi; Golbaghi, Golara; Létourneau, Myriam; Patten, Shunmoogum A.; Castonguay, Annie (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 . p. 282-293. DOI: 10.1016/j.ejmech.2017.03.029.

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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:
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: 29 juin 2017 05:07
URI: http://espace.inrs.ca/id/eprint/5370

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