Novel ruthenium complex K2[Ru(dmgly)Cl4].2H2O is toxic to C6 astrocytoma cell line, but not to primary rat astrocytes

J Inorg Biochem. 2004 Dec;98(12):2168-73. doi: 10.1016/j.jinorgbio.2004.10.007.

Abstract

A novel class of ruthenium (III) complexes of formulas K[Ru(sar)2Cl2].12H2O and K2[Ru(dmgly)Cl4].2H2O, containing bidentate chelates N-methylglycine (sarcosine, sar) or N,N-dimethylglycine (dmgly) and additional chloro ligands were synthesized. The complexes have been obtained by direct reaction of ruthenium(III) chloride with corresponding bidentate ligand followed by addition of base (KOH). These new complexes were characterized by elemental analysis, IR and electronic absorption spectroscopy. As astrocytomas, the most common of all brain tumors, are still very difficult to treat, we examined the influence of newly synthesized ruthenium-based complexes, as well as the earlier synthesized analogue platinum(IV) complexes [Pt(dmgly)2Cl2], [Pt(sar)2Br2] and [Pt(dmgly)2Br2], on rat astrocytoma C6 cells in vitro. Among these complexes only K2[Ru(dmgly)Cl4].2H2O and [Pt(dmgly)2Br2] markedly inhibited the viability of non-confluent C6 cells. Furthermore, only complex K2[Ru(dmgly)Cl4].2H2O was able to reduce viability in confluent C6 cultures. Importantly, this complex was not toxic to primary rat astrocytes or macrophages. Having in mind that appropriate chemotherapy should be effective against tumor cells without harming normal tissues, complex K2[Ru(dmgly)Cl4].2H2O could be a promising agent for developing therapeutics against astrocytomas.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / chemical synthesis
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology
  • Astrocytes / drug effects*
  • Astrocytoma / drug therapy*
  • Brain Neoplasms / drug therapy*
  • Cell Line, Tumor
  • Cell Survival
  • Dose-Response Relationship, Drug
  • Drug Resistance, Neoplasm
  • Drug-Related Side Effects and Adverse Reactions
  • Growth Inhibitors / pharmacology
  • Ligands
  • Nitric Oxide / analysis
  • Nitrites / metabolism
  • Organometallic Compounds / chemical synthesis
  • Organometallic Compounds / chemistry
  • Organometallic Compounds / pharmacology*
  • Platinum / chemistry
  • Platinum / pharmacology
  • Rats
  • Ruthenium / chemistry*
  • Ruthenium / pharmacology*
  • Spectrophotometry / methods
  • Spectrophotometry, Infrared
  • Time Factors
  • Tumor Cells, Cultured

Substances

  • Antineoplastic Agents
  • Growth Inhibitors
  • Ligands
  • Nitrites
  • Organometallic Compounds
  • Nitric Oxide
  • Platinum
  • Ruthenium