Păunescu Emilia, Soudani Mylène, Clavel Catherine M, Dyson Paul J
Institut des Sciences et Ingénierie Chimiques, Ecole Polytechnique Fédérale de Lausanne (EPFL), CH-1015 Lausanne, Switzerland.
Institut des Sciences et Ingénierie Chimiques, Ecole Polytechnique Fédérale de Lausanne (EPFL), CH-1015 Lausanne, Switzerland.
J Inorg Biochem. 2017 Oct;175:198-207. doi: 10.1016/j.jinorgbio.2017.07.027. Epub 2017 Jul 28.
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.
在鉴定出一种具有依他尼酸修饰咪唑配体的钌（II）-芳烃配合物后，该配合物可抑制谷胱甘肽转移酶（GST）并对化疗耐药癌细胞具有细胞毒性，随后制备了一系列结构相关的钌（II）-和锇（II）-对异丙基苯化合物。在这些配合物中，依他尼酸通过适当修饰的吡啶配体与金属相连。用具有一个金属中心和两个依他尼酸部分的衍生物对金属中心和金属：依他尼酸比例对化合物细胞毒性的影响进行了评估，这些衍生物对化疗耐药的A2780cisR细胞（对顺铂获得性耐药的人卵巢癌细胞）最具活性。此外，与具有依他尼酸修饰咪唑配体的配合物（RAIMID-EA，图2）相比，这些配合物表现出显著程度的癌细胞特异性。
