title: Ternary copper(II) complexes with amino acid chains and heterocyclic bases: DNA binding, cytotoxic and cell apoptosis induction properties.
abstract: Nowadays, chemotherapy is a common means of oncology. However, it is difficult to find excellent chemotherapy drugs. Here we reported three new ternary copper(II) complexes which have potential chemotherapy characteristics with reduced Schiff base ligand and heterocyclic bases (TBHP), [Cu(phen)(TBHP)]H2O (1), [Cu(dpz)(TBHP)]H2O (2) and [Cu(dppz)(TBHP)]H2O (3) (phen=1,10-phenanthroline, dpz=dipyrido [3,2:2',3'-f]quinoxaline, dppz=dipyrido [3,2-a:2',3'-c]phenazine, H2TBHP=2-(3,5-di-tert-butyl-2-hydroxybenzylamino)-2-benzyl-acetic acid). The DNA-binding properties of the complexes were investigated by spectrometric titrations, ethidium bromide displacement experiments and viscosity measurements. The results indicated that the three complexes, especially the complex 13, can strongly bind to calf-thymus DNA (CT-DNA). The intrinsic binding constants Kb of the ternary copper(II) complexes with CT-DNA were 1.37×10(5), 1.81×10(5) and 3.21×10(5) for 1, 2 and 3 respectively. Comparative cytotoxic activities of the copper(II) complexes were also determined by 3-(4,5-dimethylthiazol-2yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The results showed that the ternary copper(II) complexes had significant cytotoxic activity against the human lung cancer (A549), human esophageal cancer (Eca109) and human gastric cancer (SGC7901) cell lines. Cell apoptosis were detected by AnnexinV/PI flow cytometry and by Western blotting with the protein expression of p53, Bax and Bcl-2. All the three copper complexes can effectively induce apoptosis of the three human tumor cells.
authors.affiliation: Central Laboratory, the Affiliated Yixing Hospital of Jiangsu University, Yixing, Jiangsu Province, China.
authors.forename: Tieliang
authors.initials: T
authors.lastname: Ma
authors.affiliation: Department of Physics and Chemistry, Henan Polytechnic University, Jiaozuo, Henan Province, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Xu
authors.affiliation: Department of Physics and Chemistry, Henan Polytechnic University, Jiaozuo, Henan Province, China. Electronic address: wangyuan08@hpu.edu.cn.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Breast Surgery, the Affiliated People's Hospital of Jiangsu University, Zhenjiang, Jiangsu Province, China.
authors.forename: Hao
authors.initials: H
authors.lastname: Yu
authors.affiliation: Department of Brain Surgery, the Affiliated People's Hospital of Jiangsu University, Zhenjiang, Jiangsu Province, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Department of Respiratory, the Affiliated People's Hospital of Jiangsu University, Zhenjiang, Jiangsu Province, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Central Laboratory, the Affiliated Yixing Hospital of Jiangsu University, Yixing, Jiangsu Province, China.
authors.forename: Weiliang
authors.initials: W
authors.lastname: Ding
authors.affiliation: Central Laboratory, the Affiliated Yixing Hospital of Jiangsu University, Yixing, Jiangsu Province, China.
authors.forename: Wenjiao
authors.initials: W
authors.lastname: Zhu
authors.affiliation: Department of Respiratory, the Affiliated Yixing Hospital of Jiangsu University, Yixing, Jiangsu Province, China.
authors.forename: Ruhua
authors.initials: R
authors.lastname: Chen
authors.affiliation: Department of Critical Care Medicine, the Affiliated Yixing Hospital of Jiangsu University, Yixing City, Jiangsu Province, China.
authors.forename: Zhijun
authors.initials: Z
authors.lastname: Ge
authors.affiliation: Department of Cardiac & Thoracic Surgery, the Affiliated Yixing Hospital of Jiangsu University, Yixing City, Jiangsu Province, China.
authors.forename: Yongfei
authors.initials: Y
authors.lastname: Tan
authors.affiliation: Department of Physics and Chemistry, Henan Polytechnic University, Jiaozuo, Henan Province, China. Electronic address: jlxj@hpu.edu.cn.
authors.forename: Lei
authors.initials: L
authors.lastname: Jia
authors.affiliation: Department of Respiratory, the Affiliated People's Hospital of Jiangsu University, Zhenjiang, Jiangsu Province, China. Electronic address: taofengzhu@foxmail.com.
authors.forename: Taofeng
authors.initials: T
authors.lastname: Zhu
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D002417:Cattle; D045744:Cell Line, Tumor; D056831:Coordination Complexes / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D003300:Copper / Q000737:chemistry; D004247:DNA / Q000378:metabolism; D006801:Humans; D020128:Inhibitory Concentration 50; D008958:Models, Molecular; D015394:Molecular Structure; D010618:Phenanthrolines; D010619:Phenazines / Q000494:pharmacology; D012545:Schiff Bases
chemical_list: D000970:Antineoplastic Agents; D056831:Coordination Complexes; D010618:Phenanthrolines; D010619:Phenazines; D012545:Schiff Bases; D003300:Copper; D004247:DNA; C427203:calf thymus DNA; C025205:1,10-phenanthroline
keywords: AnnexinV/PI; Cell apoptosis; Cytotoxic; DNA-binding; Ternary copper(II) complexes