A new nitrosyl ruthenium complex: synthesis, chemical characterization, in vitro and in vivo antitumor activities and probable mechanism of action

Eur J Med Chem. 2011 Sep;46(9):3616-22. doi: 10.1016/j.ejmech.2011.04.064. Epub 2011 May 19.

Abstract

This study describes the synthesis of a new ruthenium nitrosyl complex with the formula [RuCl(2)NO(BPA)] [BPA = (2-hydroxybenzyl)(2-methylpyridyl)amine ion], which was synthesized and characterized by spectroscopy, cyclic voltammetry, X-ray crystallography, and theoretical calculation data. The biological studies of this complex included in vitro cytotoxic assays, which revealed its activity against two different tumor cell lines (HeLa and Tm5), with efficacy comparable to that of cisplatin, a metal-based drug that is administered in clinical treatment. The in vivo studies showed that [RuCl(2)NO(BPA)]is effective in reducing tumor mass. Also, our results suggest that the mechanism of action of [RuCl(2)NO(BPA)] includes binding to DNA, causing fragmentation of this biological molecule, which leads to apoptosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / chemistry*
  • Antineoplastic Agents / pharmacology*
  • CHO Cells
  • Cell Line, Tumor
  • Cricetinae
  • Cricetulus
  • Crystallography, X-Ray
  • Drug Screening Assays, Antitumor
  • Humans
  • Mice
  • Mice, Inbred C57BL
  • Models, Molecular
  • Ruthenium Compounds / chemistry*
  • Ruthenium Compounds / pharmacology*
  • Spectrum Analysis / methods

Substances

  • Antineoplastic Agents
  • Ruthenium Compounds