Synthesis, cellular uptake, apopotosis, cytotoxicity, cell cycle arrest, interaction with DNA and antioxidant activity of ruthenium(II) complexes

Eur J Med Chem. 2011 Aug;46(8):3282-90. doi: 10.1016/j.ejmech.2011.04.049. Epub 2011 Apr 29.

Abstract

A new ligand and two ruthenium(II) complexes [Ru(bpy)(2)(DNPIP)](ClO(4))(2)1 and [Ru(bpy)(2)(DAPIP)](ClO(4))(2)2 were synthesized and characterized. The DNA-binding constants for complexes 1 and 2 were determined to be 2.24 (±0.30) × 10(5) M(-1) (s = 1.29) and 6.34 (±0.32) × 10(4) M(-1) (s = 2.84). The photocleavage of pBR322 DNA by Ru(II) complexes was investigated. The cytotoxicity of complexes 1 and 2 were assessed against three tumor cell lines. The apoptosis and cellular uptake were studied. The retardation assay of pGL 3 plasmid DNA was explored. The cell cycle arrest was analysized by flow cytometry. The antioxidant activities of the ligand and complexes were also investigated.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 2,2'-Dipyridyl / chemistry
  • 2,2'-Dipyridyl / metabolism
  • 2,2'-Dipyridyl / pharmacology*
  • Antineoplastic Agents / chemical synthesis
  • Antineoplastic Agents / pharmacology*
  • Antioxidants / chemical synthesis
  • Antioxidants / pharmacology
  • Apoptosis / drug effects
  • Cell Cycle / drug effects*
  • Cell Line, Tumor
  • Coordination Complexes / chemical synthesis
  • Coordination Complexes / pharmacology*
  • DNA / chemistry
  • DNA / metabolism
  • DNA Cleavage / drug effects
  • Differential Thermal Analysis
  • Electrophoretic Mobility Shift Assay
  • Flow Cytometry
  • Humans
  • Intercalating Agents / chemical synthesis
  • Intercalating Agents / pharmacology*
  • Ligands
  • Liver Neoplasms / drug therapy*
  • Liver Neoplasms / pathology
  • Phenanthrolines / chemistry
  • Phenanthrolines / metabolism
  • Phenanthrolines / pharmacology*
  • Plasmids
  • Ruthenium / chemistry
  • Ruthenium / metabolism
  • Ruthenium / pharmacology*

Substances

  • Antineoplastic Agents
  • Antioxidants
  • Coordination Complexes
  • Intercalating Agents
  • Ligands
  • Phenanthrolines
  • 2,2'-Dipyridyl
  • Ruthenium
  • DNA
  • calf thymus DNA