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

• Published in: Journal of inorganic biochemistry 2014-12, Vol.141, p.17-27
• Main Authors: Liang, Jie-Wen, Wang, Yi, Du, Ke-Jie, Li, Guan-Ying, Guan, Rui-Lin, Ji, Liang-Nian, Chao, Hui
• Format: Article
• Language: English
• Subjects: Animals; Anticancer; Antineoplastic Agents - chemical synthesis; Antineoplastic Agents - pharmacology; Apoptosis; Apoptosis - drug effects; Cations, Divalent; Cattle; Cell Line, Tumor; Cell Survival - drug effects; Comet Assay; Coordination Complexes - chemical synthesis; Coordination Complexes - pharmacology; Copper - chemistry; Copper(II) complex; Cytotoxins - chemical synthesis; Cytotoxins - pharmacology; DNA - chemistry; DNA binding; DNA cleavage; DNA Fragmentation - drug effects; Glutathione - metabolism; Humans; Intercalating Agents - chemical synthesis; Intercalating Agents - pharmacology; Pyridines - chemistry; Reactive Oxygen Species - metabolism
• ISSN: 0162-0134; 1873-3344
• DOI: 10.1016/j.jinorgbio.2014.08.006

Three novel copper(II) complexes CuL1Cl2 (1) (L1=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. Three copper(II) complexes cleaved DNA efficiently in the presence of GSH and bounded to DNA through intercalation mode. They can also induce the apoptosis of HeLa cells with the participation of reactive oxygen species. [Display omitted]