title: Synthesis, crystal structure, DNA interaction and anticancer activity of tridentate copper(II) complexes.
abstract: Three new tridentate copper(II) complexes [Cu(dthp)Cl(2)] (1) (dthp=2,6-di(thiazol-2-yl)pyridine), [Cu(dmtp)Cl(2)] (2) (dmtp=2,6-di(5-methyl-4H-1,2,4-triazol-3-yl)pyridine) and [Cu(dtp)Cl(2)] (3) (dtp=2,6-di(4H-1,2,4-triazol-3-yl)pyridine) have been synthesized and characterized. Crystal structure of complex 1 shows that the complex existed as distorted square pyramid with five co-ordination sites occupied by the tridentate ligand and the two chlorine anions. Ethidium bromide displacement assay, viscosity measurements, circular dichroism studies and cyclic voltammetric experiments suggested that these complexes bound to DNA via an intercalative mode. Three Cu(II) complexes were found to efficiently cleave DNA in the presence of sodium ascorbate, and singlet oxygen ((1)O(2)) and hydrogen peroxide were proved to contribute to the DNA cleavage process. They exhibited anticancer activity against HeLa, Hep-G2 and BEL-7402 cell lines. Nuclear chromatin cleavage has also been observed with AO/EB staining assay and the alkaline single-cell gel electrophoresis (comet assay). The results demonstrated that three Cu(II) complexes cause DNA damage that can induce the apoptosis of BEL-7402 cells.
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, PR China.
authors.forename: Guan-Ying
authors.initials: GY
authors.lastname: Li
authors.forename: Ke-Jie
authors.initials: KJ
authors.lastname: Du
authors.forename: Jin-Quan
authors.initials: JQ
authors.lastname: Wang
authors.forename: Jie-Wen
authors.initials: JW
authors.lastname: Liang
authors.forename: Jun-Feng
authors.initials: JF
authors.lastname: Kou
authors.forename: Xiao-Juan
authors.initials: XJ
authors.lastname: Hou
authors.forename: Liang-Nian
authors.initials: LN
authors.lastname: Ji
authors.forename: Hui
authors.initials: H
authors.lastname: Chao
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D001205:Ascorbic Acid / Q000737:chemistry; D045744:Cell Line, Tumor; D002942:Circular Dichroism; D020552:Comet Assay; D056831:Coordination Complexes / Q000138:chemical synthesis* / Q000494:pharmacology; D003300:Copper / Q000737:chemistry*; D018360:Crystallography, X-Ray; D004247:DNA / Q000737:chemistry*; D053837:DNA Cleavage / Q000187:drug effects; D004996:Ethidium; D006801:Humans; D007364:Intercalating Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D008958:Models, Molecular; D010084:Oxidation-Reduction; D011725:Pyridines / Q000138:chemical synthesis* / Q000494:pharmacology; D026082:Singlet Oxygen / Q000737:chemistry
chemical_list: D000970:Antineoplastic Agents; D056831:Coordination Complexes; D007364:Intercalating Agents; D011725:Pyridines; D026082:Singlet Oxygen; D003300:Copper; D004247:DNA; D004996:Ethidium; D001205:Ascorbic Acid