Combining Metal Ions and Ligands to Fight Cancer

  • Author: Rachel McGlue
  • Published Date: 01 October 2012
  • Source / Publisher: Chemistry - A European Journal/Wiley-VCH
  • Copyright: Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
thumbnail image: Combining Metal Ions and Ligands to Fight Cancer

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The anticancer drug cisplatin is often associated with adverse effects (nausea, vomiting, oto- and nephrotoxicity, neuropathy), as well as resistance. Several Ru-based chemotherapeutics show activity against cisplatin-resistant tumors and are advancing in clinical trials due to high delivery into cancer cells and low systemic toxicity.


Sulfur-containing biomolecules are thought to have negative effects on the efficacy of Pt-based anticancer drugs due to irreversible binding of the metal to intracellular thiolato ligands. Several thiol- and sulfur-based nucleophiles have been tested as chemoprotectants to modulate cisplatin nephrotoxicity. For example, sodium diethyldithiocarbamate protects against renal, gastrointestinal, and bone-marrow toxicity induced by cisplatin with no decrease in the antitumor activity. However, protecting normal tissues without inhibiting anticancer activity is challenging.


Using these properties, Dolores Fregona and colleagues, University of Padova, Italy, have designed several metal dithiocarbamato complexes that may combine the cytotoxic activity of the metal with the protective effects of a sulfur-based ligand. They now report the synthesis and in vitro cytotoxicity toward non-small-cell lung cancer of RuII and RuIII dithiocarbamato complexes, of which the RuIII complexes show significantly greater activity than cisplatin.


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Magazine of Chemistry Europe (16 European Chemical Societies)published by Wiley-VCH