Organometallic Glutathione S‑Transferase Inhibitors

A new family of organometallic p-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-p-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.