PUBLICATION
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
- Authors
- Haghdoost, M., Golbaghi, G., Létourneau, M., Patten, S.A., Castonguay, A.
- ID
- ZDB-PUB-170404-3
- Date
- 2017
- Source
- European Journal of Medicinal Chemistry 132: 282-293 (Journal)
- Registered Authors
- Patten, Shumoogum
- Keywords
- Antiproliferative activity, Cancer, In vivo toxicity, Lipophilicity, Ruthenium complexes, Zebrafish
- MeSH Terms
-
- Animals
- Antineoplastic Agents/chemistry*
- Antineoplastic Agents/pharmacology
- Cell Line, Tumor
- Cell Proliferation/drug effects
- Cisplatin/pharmacology
- Humans
- Hydrophobic and Hydrophilic Interactions
- Ligands
- Nitrogen Oxides
- Organometallic Compounds/chemistry*
- Organometallic Compounds/pharmacology
- Ruthenium/chemistry*
- Structure-Activity Relationship
- Zebrafish/embryology
- PubMed
- 28371640 Full text @ Eur. J. Med. Chem.
Citation
Haghdoost, M., Golbaghi, G., Létourneau, M., Patten, S.A., Castonguay, A. (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. 132:282-293.
Abstract
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping