title: The structures, cytotoxicity, apoptosis and molecular docking controlled by the aliphatic chain of palladium(II) complexes.
abstract: A new series of Pd(II) complexes derived from benzenealkyl dicarboxylate ligands, [Pd(Ln)(phen)] (phen=2,9-dimethyl-1,10-phenanthroline, complex 1: L1=phenylmalonate; complex 2: L2=benzylmalonate; complex 3: L3=(2-phenylethyl)malonate; complex 4: L4=(3-phenylpropyl)malonate) have been synthesized under room temperature condition. These complexes contain a long dicarboxylate aliphatic chain. They were characterized by elemental analysis, infrared spectroscopy, single crystal X-ray diffraction. The binding of complexes with fish sperm DNA (FS-DNA) was investigated by UV absorption and fluorescence spectra. Gel electrophoresis assay demonstrated the ability of the complexes to cleave the pBR322 plasmid DNA. The cytotoxic activity of the complexes was tested against two different cancer cell lines, HeLa and HL-60. Cytotoxic activity studies showed the four complexes exhibited significant cancer cell inhibitory rate. Further flow cytometry experiments showed that the cytotoxic Pd(II) complexes induced apoptosis of HL-60 tumor cell lines. The molecular dynamic simulations and docking methods were used to predict the DNA binding affinity of Pd(II) complexes by the resulting relative binding energy of complexes with DNA -6.01, -6.25, -7.24 and -7.59 kcal/mol, while with DNA-topoisomerase I (Topo I) -7.98, -9.25, -10.2 and -11.5 kcal/mol, respectively. The good visualization images supported with the experimental results of structure-activity relationship between cytotoxicity and carbon chain length.
authors.affiliation: College of Chemistry, Liaoning University, Shenyang 110036, PR China; The key Laboratory of the Inorganic Molecule-Based Chemistry of Liaoning Province and Laboratory of Coordination Chemistry, Shenyang University of Chemical Technology, Shenyang 110142, PR China.
authors.forename: MingChang
authors.initials: M
authors.lastname: Zhu
authors.affiliation: School of Chemical Engineering, Tianjin University, Tianjin 300072, PR China.
authors.forename: Xiaoting
authors.initials: X
authors.lastname: Cui
authors.affiliation: The key Laboratory of the Inorganic Molecule-Based Chemistry of Liaoning Province and Laboratory of Coordination Chemistry, Shenyang University of Chemical Technology, Shenyang 110142, PR China.
authors.forename: Shaozhong
authors.initials: S
authors.lastname: Zhang
authors.affiliation: The key Laboratory of the Inorganic Molecule-Based Chemistry of Liaoning Province and Laboratory of Coordination Chemistry, Shenyang University of Chemical Technology, Shenyang 110142, PR China.
authors.forename: Lei
authors.initials: L
authors.lastname: Liu
authors.affiliation: College of Chemistry, Liaoning University, Shenyang 110036, PR China. Electronic address: ceshzb@lnu.edu.cn.
authors.forename: ZhengBo
authors.initials: Z
authors.lastname: Han
authors.affiliation: The key Laboratory of the Inorganic Molecule-Based Chemistry of Liaoning Province and Laboratory of Coordination Chemistry, Shenyang University of Chemical Technology, Shenyang 110142, PR China. Electronic address: ejgao@syuct.edu.cn.
authors.forename: EnJun
authors.initials: E
authors.lastname: Gao
mesh_terms: D017209:Apoptosis; D018360:Crystallography, X-Ray; D005434:Flow Cytometry; D018922:HL-60 Cells; D006801:Humans; D062105:Molecular Docking Simulation; D010165:Palladium / Q000737:chemistry*; D013057:Spectrum Analysis / Q000379:methods
chemical_list: D010165:Palladium
keywords: Apoptosis; Cytotoxicity; DNA binding; Molecular docking; Pd(II) complexes