New Luminescent Polynuclear Metal Complexes with Anticancer Properties: Toward Structure-Activity Relationships

Margot Wenzel, Andreia De Almeida, Emilia Bigaeva, Paul Kavanagh, Michel Picquet, Pierre Le Gendre, Ewen Bodio*, Angela Casini

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

47 Citations (Scopus)

Abstract

A series of new heterodinuclear luminescent complexes with two different organic ligands have been synthesized and characterized. A luminescent RuII(polypyridine) moiety and a metal-based anticancer fragment (AuCl, (p-cymene)RuCl2, (p-cymene)OsCl2, (Cp∗)RhCl2, or Au-thioglucose) are the two general features of these complexes. All of the bimetallic compounds have been evaluated for their antiproliferative properties in vitro in human cancer cell lines. Only the complexes containing an Au(I) fragment exhibit antiproliferative activity in the range of cisplatin or higher. The photophysical and electrochemical properties of the bimetallic species have been investigated, and fluorescence microscopy experiments have been performed successfully. The most promising bimetallic cytotoxic complexes (i.e., with the Au-thioglucose scaffold) have shown to be easily taken up by cancer cells at 37 °C in the cytoplasm or in specific organelles. Interestingly, experiments repeated at 4 °C showed no uptake of the bimetallic species inside cells, which confirms involvement of active transport processes. To evaluate the role of glucose transporters in the cell uptake of the gold complexes, inhibition of the GluT-1 (glucose transporter isoform with high level of expression in cancer cells) was achieved, showing only scarce influence on the compounds' uptake. Finally, the observed absence of interactions with nucleic acid model structures suggests that the gold compounds may have different intracellular targets with respect to cisplatin.

Original languageEnglish
Pages (from-to)2544-2557
Number of pages14
JournalInorganic Chemistry
Volume55
Issue number5
Early online date11 Feb 2016
DOIs
Publication statusPublished - 07 Mar 2016

ASJC Scopus subject areas

  • Inorganic Chemistry
  • Physical and Theoretical Chemistry

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