title: Synthesis, DNA interaction and anticancer activity of copper(II) complexes with 4'-phenyl-2,2':6',2″-terpyridine derivatives.
abstract: Three novel copper(II) complexes CuL(1)Cl2 (1) (L(1)=4'-(3-methoxyphenyl)-2,2':6'- 2″-terpyridine), CuL(2)Cl2 (2) (L(2)=4'-(4-methoxyphenyl)-2,2':6'-2″-terpyridine) and CuL(3)Cl2 (3) (L(3)=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.
authors.affiliation: MOE Laboratory of Bioinorganic and Synthetic Chemistry, State Key Laboratory of Optoelectronic Materials and Technologies, School of Chemistry and Chemical Engineering, Sun Yat-Sen University, Guangzhou 510275, P. R. China.
authors.forename: Jie-Wen
authors.initials: JW
authors.lastname: Liang
authors.affiliation: MOE Laboratory of Bioinorganic and Synthetic Chemistry, State Key Laboratory of Optoelectronic Materials and Technologies, School of Chemistry and Chemical Engineering, Sun Yat-Sen University, Guangzhou 510275, P. R. China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Wang
authors.affiliation: MOE Laboratory of Bioinorganic and Synthetic Chemistry, State Key Laboratory of Optoelectronic Materials and Technologies, School of Chemistry and Chemical Engineering, Sun Yat-Sen University, Guangzhou 510275, P. R. China.
authors.forename: Ke-Jie
authors.initials: KJ
authors.lastname: Du
authors.affiliation: MOE Laboratory of Bioinorganic and Synthetic Chemistry, State Key Laboratory of Optoelectronic Materials and Technologies, School of Chemistry and Chemical Engineering, Sun Yat-Sen University, Guangzhou 510275, P. R. China.
authors.forename: Guan-Ying
authors.initials: GY
authors.lastname: Li
authors.affiliation: MOE Laboratory of Bioinorganic and Synthetic Chemistry, State Key Laboratory of Optoelectronic Materials and Technologies, School of Chemistry and Chemical Engineering, Sun Yat-Sen University, Guangzhou 510275, P. R. China.
authors.forename: Rui-Lin
authors.initials: RL
authors.lastname: Guan
authors.affiliation: MOE Laboratory of Bioinorganic and Synthetic Chemistry, State Key Laboratory of Optoelectronic Materials and Technologies, School of Chemistry and Chemical Engineering, Sun Yat-Sen University, Guangzhou 510275, P. R. China.
authors.forename: Liang-Nian
authors.initials: LN
authors.lastname: Ji
authors.affiliation: MOE Laboratory of Bioinorganic and Synthetic Chemistry, State Key Laboratory of Optoelectronic Materials and Technologies, School of Chemistry and Chemical Engineering, Sun Yat-Sen University, Guangzhou 510275, P. R. China. Electronic address: ceschh@mail.sysu.edu.cn.
authors.forename: Hui
authors.initials: H
authors.lastname: Chao
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D002413:Cations, Divalent; D002417:Cattle; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D020552:Comet Assay; D056831:Coordination Complexes / Q000138:chemical synthesis* / Q000494:pharmacology; D003300:Copper / Q000737:chemistry*; D003603:Cytotoxins / Q000138:chemical synthesis* / Q000494:pharmacology; D004247:DNA / Q000737:chemistry; D053938:DNA Fragmentation / Q000187:drug effects; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D007364:Intercalating Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D011725:Pyridines / Q000737:chemistry*; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D002413:Cations, Divalent; D056831:Coordination Complexes; D003603:Cytotoxins; D007364:Intercalating Agents; D011725:Pyridines; D017382:Reactive Oxygen Species; D003300:Copper; D004247:DNA; C427203:calf thymus DNA; D005978:Glutathione
keywords: Anticancer; Apoptosis; Copper(II) complex; DNA binding; DNA cleavage