Synthesis, characterization, antiproliferative and anti-metastatic properties of two ruthenium-DMSO complexes containing 2,2'-biimidazole

Eur J Med Chem. 2011 May;46(5):1555-63. doi: 10.1016/j.ejmech.2011.01.074. Epub 2011 Feb 26.

Abstract

Two new ruthenium complexes, trans,cis,cis-[RuCl2(DMSO)2(H2biim)] (1) and mer-[RuCl3(DMSO)(H2biim)] (2) (DMSO=dimethyl sulfoxide and H2biim=2,2'-biimidazole), have been synthesized and fully characterized by single-crystal X-ray analysis. The less stable complex 2 is more cytotoxic against the four human cancer cell lines tested than 1. Further studies show that 1 and 2 exhibit cell growth inhibition by triggering G0/G1 cell cycle arrest and mitochondria-mediated apoptosis. Additionally, complex 2 exerts potent inhibitory effects on the adhesion and migration of human cancer cells comparable to that of NAMI-A ([ImH][trans-[RuCl4(Im)(DMSO-S)], Im=imidazole). Target validation studies show that cyclin-dependent kinases (CDKs), other than DNA, are more likely to be targets of 1 and 2.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / chemical synthesis
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology*
  • Apoptosis / drug effects
  • Cell Adhesion / drug effects
  • Cell Cycle / drug effects
  • Cell Line, Tumor
  • Cell Movement / drug effects
  • Cell Proliferation / drug effects
  • Crystallography, X-Ray
  • Dimethyl Sulfoxide / chemistry*
  • Drug Screening Assays, Antitumor
  • HeLa Cells
  • Humans
  • Imidazoles / chemistry*
  • Models, Molecular
  • Molecular Structure
  • Organometallic Compounds / chemical synthesis
  • Organometallic Compounds / chemistry
  • Organometallic Compounds / pharmacology*
  • Ruthenium / chemistry*
  • Stereoisomerism
  • Structure-Activity Relationship

Substances

  • Antineoplastic Agents
  • Imidazoles
  • Organometallic Compounds
  • 2,2'-biimidazole
  • Ruthenium
  • Dimethyl Sulfoxide