Synthesis, DNA interaction and anticancer activity of copper(II) complexes with 4′-phenyl-2,2′:6′,2″-terpyridine derivatives

Three novel copper(II) complexes CuL¹Cl₂ (1) (L ¹ = 4′-(3-methoxyphenyl)-2,2′:6′- 2″-terpyridine), CuL²Cl₂ (2) (L² = 4′-(4-methoxyphenyl)-2,2′:6′-2″-terpyridine) and CuL³Cl₂ (3) (L³ = 4′-(3,5- dimethoxyphenyl)-2,2′:6′-2″-terpyridine) have been synthesized and characterized. Absorption spectral titration experiments, ethidium bromide displacement assays, and cyclic voltammetric experiments were carried out and the results suggested that these complexes bound to DNA through an intercalative mode. Moreover, these complexes were found to cleave pBR322 DNA efficiently in the presence of glutathione (GSH), and exhibited good anticancer activity against HeLa, Hep-G2 and BEL-7402 cell lines. Nuclear chromatin cleavage was also observed by acridine orange/ethidium bromide (AO/EB) staining assays and comet assays. These results demonstrated that these three Cu(II) complexes caused DNA damage and induced the apoptosis of HeLa cells. Mechanistic investigations revealed the participation of reactive oxygen species which can be trapped by reactive oxygen species (ROS) radical scavengers and ROS sensors.