DNA interaction, antioxidant activity, and bioactivity studies of two ruthenium(II) complexes

Spectrochim Acta A Mol Biomol Spectrosc. 2015 Jan 25:135:840-9. doi: 10.1016/j.saa.2014.07.075. Epub 2014 Aug 8.

Abstract

Two new ruthenium(II) polypyridyl complexes [Ru(dmb)2(dcdppz)](ClO4)2 (1) and [Ru(bpy)2(dcdppz)](ClO4)2 (2) were prepared and characterized. The crystal structure of the complex 2 was solved by single crystal X-ray diffraction. The complex crystallizes in the monoclinic system, space group P21/n with a=12.9622(14)Å, b=17.1619(19)Å, c=22.7210(3)Å, β=100.930(2)(°), R=0.0536, Rω=0.1111. The DNA-binding constants for complexes 1 and 2 were determined to be 1.92×10(5) (s=1.72) and 2.24×10(5) (s=1.86)M(-1), respectively. The DNA-binding behaviors showed that complexes 1 and 2 interact with DNA by intercalative mode. The antioxidant activities of the ligand and the complexes were performed. Ligand, dcdppz, has no cytotoxicity against the selected cell lines. Complex 1 shows higher cytotoxicity than complex 2, but lower than cisplatin toward selected cell lines. The apoptosis and cell cycle arrest were investigated, and the apoptotic mechanism of BEL-7402 cells was studied by reactive oxygen species (ROS), mitochondrial membrane potential and western blot analysis. Complex 1 induces apoptosis in BEL-7402 cells through ROS-mediated mitochondrial dysfunction pathway and by regulating the expression of Bcl-2 family proteins.

Keywords: Apoptosis; DNA-binding; Mitochondrial membrane potential; Ruthenium(II) complex; Western blot analysis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antioxidants / pharmacology*
  • Apoptosis / drug effects
  • Caspases / metabolism
  • Cattle
  • Cell Cycle / drug effects
  • Cell Death / drug effects
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Coordination Complexes / chemical synthesis
  • Coordination Complexes / chemistry
  • Coordination Complexes / pharmacology*
  • Crystallography, X-Ray
  • DNA / metabolism*
  • Electrons
  • Endocytosis / drug effects
  • Flow Cytometry
  • Free Radical Scavengers / pharmacology
  • Humans
  • Hydroxyl Radical / chemistry
  • Inhibitory Concentration 50
  • Ligands
  • Luminescence
  • Membrane Potential, Mitochondrial / drug effects
  • Molecular Conformation
  • Neoplasm Proteins / metabolism
  • Ruthenium / pharmacology*
  • Spectrometry, Fluorescence
  • Viscosity

Substances

  • Antioxidants
  • Coordination Complexes
  • Free Radical Scavengers
  • Ligands
  • Neoplasm Proteins
  • Hydroxyl Radical
  • Ruthenium
  • DNA
  • calf thymus DNA
  • Caspases