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

Abstract

A series of new heterodinuclear luminescent complexes with two different organic ligands have been synthesized and characterized. A luminescent Ru(II)(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.

Heterobimetallic Complexes for Theranostic Applications

“…Thus, other explored examples included within the group of d 6 ‐bifunctional probes are those heterobimetallic complexes using Ru II derivatives as luminophores. Specifically, Ru II complexes of the type [Ru(N^N) 3 ] 2+ coupled to either Au I or Ru II derivatives, emulating the well‐known bioactive auranofin or RAPTA‐T, respectively, or just combined with novel potential, for example, Au I /Ag I ‐NHC‐based therapeutics . Figure exemplifies the importance of a thorough design to deliver an optimized bioprobe.…”

“…Since then, and seeing the successo ft he proposed concept, "heterobimetallic species as opticalt heranostic agents", analogous examples were reported in the literature that highlight the potential of the approach. Thus, other explored examples included within the group of d 6 -bifunctional probes are those heterobimetallic complexes using Ru II derivatives as luminophores.S pecifically,R u II complexes of the type [Ru(N^N) 3 ] 2 + coupled to either Au I or Ru II derivatives, emulatingt he wellknownb ioactive auranofin or RAPTA-T,r espectively, [33] or just combined with novel potential, for example, Au I /Ag I -NHCbased therapeutics. [34] Figure9exemplifies the importanceo fa Figure 7.…”

“…[32] Figure 9. Heterobimetallictrackable probesd erived from luminescentRu II complexes.R eprinted with permissionfrom Ref [33].Copyright2 016,American ChemicalS ociety.…”

Drug-target interaction prediction: A Bayesian ranking approach

“…into account and make DTI predictions for those conditions. For example, Wenzel et al [54] reported that their bimetallic cytotoxic complexes were shown to be easily taken up by cancer cells at 37 °C, whereas experiments at 4 °C showed no uptake. Incorporation of the aforementioned conditions into DTI prediction methods, in order to allow for more specific predictions, is left for future work.…”

Synthesis, Theory and In Vitro Photodynamic Activities of New Copper(II)‐Histidinito Complexes

“…Structural versatility along with interesting redox and photo‐chemistry has translated transition metal complexes into viable alternative of porphyrin‐based PDT agents . The photo‐activated transition metal complexes, often leading to ligand exchange, intramolecular redox reaction or generation of various ROS through energy transfer to molecular oxygenare of particular interest in developing metal‐based photo‐chemotherapeuticagents . Recently, complexes of bio‐compatible first row transition metals with low energy charge transfer or d‐d band have been extensively explored for visible light induced cytotoxicity .…”