Evaluation of DNA binding, DNA cleavage, protein binding and in vitro cytotoxic activities of bivalent transition metal hydrazone complexes

Eur J Med Chem. 2011 Aug;46(8):3376-87. doi: 10.1016/j.ejmech.2011.05.001. Epub 2011 May 8.

Abstract

Divalent Co, Ni and Cu hydrazone complexes containing [N'-(phenyl(pyridine-2-yl)methylidene) benzohydrazide] ligand were synthesised and characterised. Interactions of these complexes with DNA revealed an intercalative mode of binding between them. Further, all the hydrazone chelates showed moderate ability to cleave pUC19 DNA. Synchronous fluorescence spectra proved that the interaction of metal complexes with bovine serum albumin (BSA) resulted in a conformational change of the latter. Assay on the cytotoxicity of the above complexes against HeLa tumor cells and NIH 3T3 normal cells revealed that the complexes are toxic only against tumor cells but not to normal cells. In all the biological assays, the complex with copper ion as the metal center showed enhanced activities than the other two.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / chemical synthesis*
  • Antineoplastic Agents / pharmacology
  • Breast Neoplasms / drug therapy
  • Breast Neoplasms / pathology
  • Cattle
  • Cobalt / chemistry
  • Cobalt / metabolism
  • Coordination Complexes / chemical synthesis*
  • Coordination Complexes / pharmacology
  • Copper / chemistry*
  • Copper / metabolism
  • Crystallography, X-Ray
  • DNA / metabolism
  • DNA Cleavage / drug effects
  • Female
  • HeLa Cells
  • Humans
  • Hydrazones / chemical synthesis*
  • Hydrazones / pharmacology
  • Intercalating Agents / chemical synthesis*
  • Intercalating Agents / pharmacology
  • Mice
  • Models, Molecular
  • NIH 3T3 Cells
  • Nickel / chemistry
  • Nickel / metabolism
  • Plasmids / metabolism
  • Protein Binding / drug effects
  • Protein Conformation / drug effects
  • Pyridines / chemistry
  • Serum Albumin, Bovine / chemistry*
  • Serum Albumin, Bovine / metabolism
  • Spectrometry, Fluorescence

Substances

  • Antineoplastic Agents
  • Coordination Complexes
  • Hydrazones
  • Intercalating Agents
  • Pyridines
  • Serum Albumin, Bovine
  • Cobalt
  • Copper
  • Nickel
  • DNA