Effect of coordinated ligands on antiproliferative activity and DNA cleavage property of three mononuclear Cu(II)-terpyridine complexes

Eur J Med Chem. 2012 Nov:57:449-58. doi: 10.1016/j.ejmech.2012.06.039. Epub 2012 Jul 16.

Abstract

Three mononuclear copper(II) complexes, [Cu(tpy)Cl(2)] 1, [Cu(tpy)(NO(3))(2)(H(2)O)] 2 and [Cu(Ptpy)Cl(2)]·H(2)O·HCl 3 have been synthesised and characterized by various spectroscopic techniques and single crystal X-ray diffraction. Complexes 1 and 3 have five coordinate geometry in solid state, whereas complex 2 has six coordinate geometry. Mass spectral and EPR evidence suggest that in solution all the three complexes exist predominantly as a four coordinate species. Molecular modelling and DNA cleavage studies indicate that complexes 1 and 2 are DNA minor groove binders, whereas 3 is an intercalator. All the three complexes show nuclease activity in the presence of hydrogen peroxide. The three complexes have been found to be cytotoxic towards A549 lung adenocarcinoma cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / drug therapy
  • Adenocarcinoma / metabolism
  • Adenocarcinoma of Lung
  • Antineoplastic Agents / chemical synthesis*
  • Antineoplastic Agents / pharmacology
  • Apoptosis / drug effects
  • Binding Sites
  • Cell Cycle / drug effects
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Coordination Complexes / chemical synthesis*
  • Coordination Complexes / pharmacology
  • Copper / chemistry*
  • Crystallography, X-Ray
  • DNA / chemistry
  • DNA / metabolism*
  • DNA Cleavage
  • DNA, Superhelical / chemistry
  • DNA, Superhelical / metabolism*
  • Deoxyribonucleases / chemistry
  • Deoxyribonucleases / metabolism
  • Electron Spin Resonance Spectroscopy
  • Humans
  • Hydrogen Peroxide / metabolism
  • Lung Neoplasms / drug therapy
  • Lung Neoplasms / metabolism
  • Mass Spectrometry
  • Molecular Docking Simulation
  • Plasmids
  • Pyridines / chemistry*

Substances

  • Antineoplastic Agents
  • Coordination Complexes
  • DNA, Superhelical
  • Pyridines
  • Copper
  • DNA
  • calf thymus DNA
  • Hydrogen Peroxide
  • Deoxyribonucleases