title: Study on potential antitumor mechanism of a novel Schiff base copper(II) complex: synthesis, crystal structure, DNA binding, cytotoxicity and apoptosis induction activity.
abstract: A new cytotoxic copper(II) complex with Schiff base ligand [Cu(II)(5-Cl-pap)(OAc)(H(2)O)]·2H(2)O (1) (5-Cl-pap=N-2-pyridiylmethylidene-2-hydroxy-5-chloro-phenylamine), was synthesized and structurally characterized by X-ray diffraction. Single-crystal analysis revealed that the copper atom shows a 4+1 pyramidal coordination, a water oxygen appears in the apical position, and three of the basal positions are occupied by the NNO tridentate ligand and the fourth by an acetate oxygen. The interaction of Schiff base copper(II) complex 1 with DNA was investigated by UV-visible spectra, fluorescence spectra and agarose gel electrophoresis. The apparent binding constant (K(app)) value of 6.40×10(5) M(-1) for 1 with DNA suggests moderate intercalative binding mode. This copper(II) complex displayed efficient oxidative cleavage of supercoiled DNA, which might indicate that the underlying mechanism involve hydroxyl radical, singlet oxygen-like species, and hydrogen peroxide as reactive oxygen species. In addition, our present work showed the antitumor effect of 1 on cell cycle and apoptosis. Flow cytometric analysis revealed that HeLa cells were arrested in the S phase after treatment with 1. Fluorescence microscopic observation indicated that complex 1 can induce apoptosis of HeLa cells, whose process was mediated by intrinsic mitochondrial apoptotic pathway owing to the activation of caspase-9 and caspase-3.
authors.affiliation: School of Pharmaceutical Sciences, Tianjin Medical University, Tianjin, PR China.
authors.forename: Xin
authors.initials: X
authors.lastname: Qiao
authors.forename: Zhong-Ying
authors.initials: ZY
authors.lastname: Ma
authors.forename: Cheng-Zhi
authors.initials: CZ
authors.lastname: Xie
authors.forename: Fei
authors.initials: F
authors.lastname: Xue
authors.forename: Yan-Wen
authors.initials: YW
authors.lastname: Zhang
authors.forename: Jing-Yuan
authors.initials: JY
authors.lastname: Xu
authors.forename: Zhao-Yan
authors.initials: ZY
authors.lastname: Qiang
authors.forename: Jian-Shi
authors.initials: JS
authors.lastname: Lou
authors.forename: Gong-Jun
authors.initials: GJ
authors.lastname: Chen
authors.forename: Shi-Ping
authors.initials: SP
authors.lastname: Yan
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000633:toxicity*; D017209:Apoptosis; D053148:Caspase 3 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D045744:Cell Line, Tumor; D056831:Coordination Complexes / Q000138:chemical synthesis / Q000737:chemistry* / Q000633:toxicity*; D003300:Copper / Q000737:chemistry; D018360:Crystallography, X-Ray; D004247:DNA / Q000737:chemistry / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D008024:Ligands; D008958:Models, Molecular; D012545:Schiff Bases / Q000737:chemistry; D013050:Spectrometry, Fluorescence
chemical_list: D000970:Antineoplastic Agents; D056831:Coordination Complexes; D008024:Ligands; D012545:Schiff Bases; D003300:Copper; D004247:DNA; D053148:Caspase 3; D053453:Caspase 9