Synthesis and anticancer activity of mixed ligand 3d metal complexes

Abstract

Our previously reported copper-based complexes of tropolone show nice antitumor effects, but with high cytotoxicity to normal cells, which is presumably caused by copper ions. Here we managed to achieve this challenge by using other 3d metals to replace copper ions. We thus prepared four mononuclear 3d Metal complexes [M(phen)L2] (M = Mn, Co, Ni, Zn for 1–4, respectively). Complexes 1 and 4 show selectivity on different cancer cell lines with much lower cytotoxicity to normal cells than cisplatin. The anti-cancer effects for complexes 2 and 3 on the tested cancer cell lines are very poor. It revealed a tuning effect of different metal ions on the anti-cancer activities with that for Mn(II) and Zn(II) being much higher than that for Co(II) and Ni(II) in this system. Among of them, complex 1 presents a best anti-cancer effect on Hela cells comparable to cisplatin. It overcame the afore-mentioned shortage of high cytotoxicity to normal cells for the reported Cu(II) complexes. It revealed from the mechanistic studies that complex 1 mainly induces apoptosis through the mitochondrial pathway by increasing intracellular ROS, releasing Ca2+, activating Caspase 9 and pro-apoptotic gene Bax.