Cytotoxic properties of a new organometallic platinum(II) complex and its gold(I) heterobimetallic derivatives

Dalton Trans. 2016 Jan 14;45(2):579-90. doi: 10.1039/c5dt02714d.

Abstract

A novel platinum(ii) organometallic complex, [Pt(pbi)(Me)(DMSO)], bearing the 2-(2'-pyridyl)-benzimidazole (pbiH) ligand, was synthesized and fully characterized. Interestingly, the reaction of this organometallic platinum(ii) complex with two distinct gold(i) phosphane compounds afforded the corresponding heterobimetallic derivatives with the pbi ligand bridging the two metal centers. The antiproliferative properties in vitro of [Pt(pbi)(Me)(DMSO)] and its gold(i) derivatives as well as those of the known coordination platinum(ii) and palladium(ii) complexes with the same ligand, of the general formula [MCl2(pbiH)], were comparatively evaluated against A2780 cancer cells, either sensitive or resistant to cisplatin. A superior biological activity of the organometallic compound clearly emerged compared to the corresponding platinum(ii) complex; the antiproliferative effects are further enhanced upon attaching the gold(i) triphenylphosphine moiety to the organometallic Pt compound. Remarkably, these novel metal species are able to overcome nearly complete resistance to cisplatin. Significant mechanistic insight into the study compounds was gained after investigating their reactions with a few representative biomolecules by electrospray mass spectrometry and X-ray crystallography. The obtained results are comprehensively discussed.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / chemical synthesis
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology
  • Binding Sites
  • Catalytic Domain
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Coordination Complexes / chemical synthesis
  • Coordination Complexes / chemistry*
  • Coordination Complexes / pharmacology
  • Crystallography, X-Ray
  • Eosinophil Cationic Protein / chemistry
  • Eosinophil Cationic Protein / metabolism
  • Gold / chemistry*
  • Humans
  • Inhibitory Concentration 50
  • Molecular Dynamics Simulation
  • Platinum / chemistry*
  • Spectrometry, Mass, Electrospray Ionization
  • Spectrophotometry, Ultraviolet

Substances

  • Antineoplastic Agents
  • Coordination Complexes
  • Platinum
  • Gold
  • Eosinophil Cationic Protein