Cu(ii)-TACN complexes selectively induce antitumor activity in HepG-2 cells via DNA damage and mitochondrial-ROS-mediated apoptosis.

A new 1,4,7-triazacyclononane derivative, 4-benzyloxy-benzyl-1,4,7-triazacyclononane (btacn), and three associated cyclen complexes, Cu(btacn)Cl, Zn(btacn)Cl and [Cu(btacn)]·(ClO), were prepared to serve as DNA synthesis interferents. The compounds were characterized using IR, H and C NMR, ESI-MS, elemental analysis and X-ray single crystal diffraction methods, and their DNA damage mechanisms and cytotoxicities towards cancer and normal cells were studied. Among them, Cu(btacn)Cl and [Cu(btacn)]·(ClO) exhibit potent anti-proliferation activity in HepG-2 and HeLa cells, but low cytotoxicity in the normal cell models LO2 and HUVEC, giving SI values (IC ratios) ranging from 2.