Increasing anti-cancer activity with longer tether lengths of group 9 Cp* complexes

Dalton Trans. 2016 Apr 28;45(16):6812-5. doi: 10.1039/c6dt00186f.

Abstract

Here in, we report the cytotoxicity of both rhodium and iridium functionalised Cp* analogues of the [Cp*MCl2]2 dimers. The functionalised dimers contain a hydroxy tethered arm of differing carbon length. These show promising IC50 values when tested against HT-29, A2780 and cisplatin-resistant A2780cis human cancer cell lines, with the cytotoxicity improving proportionally with an increase in carbon tether length of the Cp* ring. The most promising results are seen for the 14-carbon Cp* tethered rhodium () and iridium () complexes, which show up to a 24-fold increase in IC50 compared to the unfunctionalised [Cp*MCl2]2 dimer. All complexes were potent inhibitors of purified thioredoxin reductase suggesting that disruption of cellular anti-oxidant function is one potential mechanism of action.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / chemistry*
  • Antineoplastic Agents / pharmacology*
  • Cell Proliferation / drug effects
  • Cisplatin / pharmacology
  • Drug Resistance, Neoplasm / drug effects
  • HT29 Cells
  • Humans
  • Iridium / chemistry*
  • Models, Molecular
  • Molecular Conformation
  • Organometallic Compounds / chemistry*
  • Organometallic Compounds / pharmacology*
  • Rhodium / chemistry*
  • Structure-Activity Relationship

Substances

  • Antineoplastic Agents
  • Organometallic Compounds
  • Iridium
  • Rhodium
  • Cisplatin