A facile route to Pt-II complexes doubly functionalized with bioactive molecules through a bipyridine-type ligand is described. Initially, ligands L-EE (containing two ethacrynic acid units), L-EF (ethacrynic acid+flurbiprofen) and L-EB (ethacrynic acid+biotin) were obtained in moderate to good yields from 2,2 '-bipyridine-4,4 '-dicarboxylic acid. Subsequent reaction of the ligands with [PtCl2(DMSO)(2)] afforded complexes [PtCl2(L-EE)] (2), [PtCl2(L-EF)] (3) and [PtCl2(L-EB)] (4) in high yields. All compounds were fully characterized by analytical and spectroscopic methods. Complexes 2-4 are highly stable in water/DMSO solution at 37 degrees C after 72 h, whereas progressive release of the bioactive fragments was detected in a cell culture medium. The compounds were assessed for their in vitro antiproliferative activity towards tumorigenic A2780, A2780cisR and Y79 cells and non-tumourigenic HEK293 cells. In particular, the combination of ethacrynic acid and flurbiprofen in 3 overcomes cisplatin-based resistance and provides strong cancer cell selectivity. Enzyme inhibition assays on human GST P1 and human COX-2 and cross-experiments with complex 1, analogous to 2-4 but lacking bio-groups, revealed a clear synergy between the Pt-II frame and the bioactive organic components.