Organometallic Glutathione <i>S</i>‑Transferase Inhibitors

A new family of organometallic <i>p</i>-cymene ruthenium­(II) and osmium­(II) complexes conjugated to ethacrynic acid, a glutathione transferase (GST) inhibitor, is reported. The ethacrynic acid moiety (either one or two) is tethered to the arene ruthenium­(II) and osmium­(II) fragments via strongly coordinating modified bipyridine ligands. The solid-state structure of one of the complexes, i.e. [Os­(η⁶-<i>p</i>-cymene)­Cl]­[(4′-methyl-[2,2′-bipyridin]-4-yl)­methyl-2-(2,3-dichloro-4-(2-methylenebutanoyl)­phenoxy)­acetate]­Cl, was established by single-crystal X-ray diffraction, corroborating the expected structure. The complexes are efficient inhibitors of GST P1-1, an enzyme expressed in cancer cells and implicated in drug resistance, and are cytotoxic to the GST-overexpressing chemoresistant A2780cisR ovarian cancer cell line

Discovery of a Highly Tumor-Selective Organometallic Ruthenium(II)–Arene Complex

A ruthenium­(II)–arene complex with a perfluoroalkyl-ligand was found to display remarkable selectivity toward cancer cells. IC₅₀ values on several cancer cell lines are in the range of 25–45 μM, and no cytotoxic effect was observed on nontumorigenic (HEK-293) cells at concentrations up to 500 μM (the maximum concentration tested). Consequently, this complex was used as the basis for the development of a number of related derivatives, which were screened in cancerous and noncancerous cell lines. The lead compound was then evaluated in vivo for antiangiogenic activity in the CAM model and in a xenografted ovarian carcinoma tumor (A2780) grown on the CAM. A 90% reduction in the tumor growth was observed