Varying the metal to ethacrynic acid ratio in ruthenium(ii)/osmium(ii)-p-cymene conjugates
Following the identification of a ruthenium(II)-arene complex with an ethacrynic acid-modified imidazole ligand, which inhibits glutathione transferase (GST) and is cytotoxic to chemo-resistant cancer cells, a series of structurally related ruthenium(II)- and osmium(II)-p-cymene compounds have been...
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Published in | Journal of inorganic biochemistry Vol. 175; pp. 198 - 207 |
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Main Authors | , , , |
Format | Journal Article |
Language | English |
Published |
United States
Elsevier Inc
01.10.2017
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Subjects | |
Online Access | Get full text |
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Summary: | Following the identification of a ruthenium(II)-arene complex with an ethacrynic acid-modified imidazole ligand, which inhibits glutathione transferase (GST) and is cytotoxic to chemo-resistant cancer cells, a series of structurally related ruthenium(II)- and osmium(II)-p-cymene compounds have been prepared. In these complexes the ethacrynic acid is linked to the metals via appropriately modified pyridine ligands. The influence of the metal center and the metal:ethacrynic acid ratio on the cytotoxicity of the compounds was evaluated with the derivatives with one metal center and two ethacrynic acid moieties being the most potent against chemo-resistant A2780cisR cells (human ovarian cancer cells with acquired resistance to cisplatin). Moreover, compared to a complex with an ethacrynic acid-modified imidazole ligand (RAIMID-EA, Figure 2), these complexes display a significant degree of cancer cell specificity.
In a series of organometallic anticancer compounds conjugated to ethacrynic acid, a potent glutathione transferase inhibitor, the influence of the metal:ethacrynic acid ratio on cytotoxicity is assessed. [Display omitted]
•New ethacrynic acid-modified ligands and associated organometallic complexes reported.•Influence of the metal (Ru vs Os) and the metal:ethacrynic acid ratio on cytotoxicity determined.•Metal:ethacrynic acid ratio 1:2 leads to the most active compounds.•Compounds are active against cisplatin-resistant human ovarian cancer cells. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 0162-0134 1873-3344 |
DOI: | 10.1016/j.jinorgbio.2017.07.027 |