Synthesis, DNA-binding and topoisomerase inhibitory activity of ruthenium(II) polypyridyl complexes

Eur J Med Chem. 2011 Apr;46(4):1056-65. doi: 10.1016/j.ejmech.2011.01.019. Epub 2011 Jan 21.

Abstract

Two ruthenium(II) complexes [Ru(bpy)(2)(bfipH)](2+) (1) and [Ru(phen)(2)(bfipH)](2+) (2) have been synthesized and characterized. The DNA-binding behaviors of complexes were studied by using spectroscopic and viscosity measurements. Results suggested that the two complexes bind to DNA in an intercalative mode. Complexes 1 and 2 can efficiently photocleave pBR322 DNA in vitro under irradiation, singlet oxygen ((1)O(2)) was proved to contribute to the DNA photocleavage process. Topoisomerase inhibition and DNA strand passage assay confirmed that two Ru(II) complexes acted as efficient dual inhibitors of topoisomerases I and II. In MTT cytotoxicity studies, two Ru(II) complexes exhibited antitumor activity against BEL-7402, HeLa, MCF-7 tumor cells. The AO/EB staining assay indicated that Ru(II) complexes could induce the apoptosis of HeLa cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cattle
  • Cell Line, Tumor
  • Crystallography, X-Ray
  • DNA / chemistry
  • DNA / metabolism*
  • DNA Cleavage / drug effects
  • DNA Cleavage / radiation effects
  • DNA Topoisomerases / metabolism*
  • Humans
  • Inhibitory Concentration 50
  • Organometallic Compounds / chemical synthesis
  • Organometallic Compounds / chemistry
  • Organometallic Compounds / metabolism*
  • Organometallic Compounds / pharmacology*
  • Ruthenium / chemistry*
  • Topoisomerase Inhibitors / chemical synthesis
  • Topoisomerase Inhibitors / chemistry
  • Topoisomerase Inhibitors / metabolism*
  • Topoisomerase Inhibitors / pharmacology*

Substances

  • Organometallic Compounds
  • Topoisomerase Inhibitors
  • Ruthenium
  • DNA
  • DNA Topoisomerases