title: Enantiopure copper(II) complex of natural product rosin derivative: DNA binding, DNA cleavage and cytotoxicity.
abstract: To develop chiral anticancer drug candidates for molecular target DNA, the synthesis and characterization of a novel enantiomerically pure copper(II) complex [Cu 1 Cl2] (2) of an optically pure ligand N-(pyridin-2-ylmethylene) dehydroabietylamine (1) was carried out. The coordination geometry of the copper center is a distorted square-planar arrangement. The interactions of 1 and 2 with salmon sperm DNA were investigated by viscosity measurements, UV, fluorescence and circular dichroism (CD) spectroscopic techniques. All the results reveal that 1 and 2 interacted with DNA through intercalation and 2 exhibited a higher DNA binding ability. Further, 1 and 2 could cleave supercoiled pBR322 DNA by single strand and 2 displayed stronger cleavage ability in the presence of ascorbic acid. In vitro cytotoxicity of 1 and 2 against HeLa, SiHa, HepG-2 and A431 cancer cell lines was studied using CCK-8 assay. The results indicate that 2 had a superior cytotoxicity than 1 and the widely used drug cisplatin under identical conditions. Flow cytometry analysis demonstrates 2 produced death of HeLa cancer cells through an apoptotic pathway. Cell cycle analysis shows that 2 mainly arrested HeLa cells at the S phase. A novel enantiomerically pure copper(II) complex [Cu 1 Cl2] (2) of an optically pure ligand N-(pyridin-2-ylmethylene) dehydroabietylamine (1), based on natural product rosin has been synthesized. 2 has the potential to act as effective anticancer drug.
authors.affiliation: College of Chemical Engineering, Nanjing Forestry University, Nanjing, 210037, China. hgfbl@njfu.edu.cn.|State Key Laboratory of Coordination Chemistry, Coordination Chemistry Institute, Nanjing University, Nanjing, 210093, China. hgfbl@njfu.edu.cn.
authors.forename: Bao-Li
authors.initials: BL
authors.lastname: Fei
authors.affiliation: College of Chemical Engineering, Nanjing Forestry University, Nanjing, 210037, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Yin
authors.affiliation: College of Chemical Engineering, Nanjing Forestry University, Nanjing, 210037, China.
authors.forename: Dong-Dong
authors.initials: DD
authors.lastname: Li
authors.affiliation: College of Chemical Engineering, Nanjing Forestry University, Nanjing, 210037, China.
authors.forename: Wu-Shuang
authors.initials: WS
authors.lastname: Xu
authors.affiliation: College of Chemical Engineering, Nanjing Forestry University, Nanjing, 210037, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Lu
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D001667:Binding, Competitive; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002942:Circular Dichroism; D056831:Coordination Complexes / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D003300:Copper / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D018360:Crystallography, X-Ray; D004247:DNA / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D006367:HeLa Cells; D056945:Hep G2 Cells; D006801:Humans; D020128:Inhibitory Concentration 50; D015394:Molecular Structure; D012116:Resins, Plant / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D013237:Stereoisomerism; D014783:Viscosity
chemical_list: D000970:Antineoplastic Agents; D056831:Coordination Complexes; D012116:Resins, Plant; D003300:Copper; C013893:rosin; D004247:DNA
keywords: Chiral copper(II) complex; Cytotoxicity; DNA binding; DNA cleavage