In vitro and in vivo antitumor activities of Ru and Cu complexes with terpyridine derivatives as ligands

Six terpyridine ligands(L1-L6) with chlorophenol or bromophenol moiety were obtained to prepare metal terpyridine derivatives complexes: [Ru(L1)(DMSO)Cl2] (1), [Ru(L2)(DMSO)Cl2] (2), [Ru(L3)(DMSO)Cl2] (3), [Cu(L4)Br2]·DMSO (4), Cu(L5)Br2 (5), and [Cu(L6)Br2]⋅CH3OH (6). The complexes were fully characterized. Ru complexes 1–3 showed low cytotoxicity against the tested cell lines. Cu complexes 4–6 exhibited higher cytotoxicity against several tested cancer cell lines compared to their ligands and cisplatin, and lower toxicity towards normal human cells. Copper(II) complexes 4–6 arrested T-24 cell cycle in G1 phase. The mechanism studies indicated that complexes 4–6 accumulated in mitochondria of T-24 cells and caused significant reduction of the mitochondrial membrane potential, increase of the intracellular ROS levels and the release of Ca2+, and the activation of the Caspase cascade, finally inducing apoptosis. Animal studies showed that complex 6 obviously inhibited the tumor growth in a mouse xenograft model bearing T-24 tumor cells without significant toxicity.