Organometallic metal(arene) anticancer agents require ligand exchange for their anticancer activity and this is generally believed to confer low selectivity for potential cellular targets. However, using an integrated proteomics-based target-response profiling approach as a potent hypothesis-generating procedure, we found an unexpected target selectivity of a ruthenium(arene) pyridinecarbothioamide (plecstatin) for plectin, a scaffold protein and cytolinker, which was validated in a plectin knock-out model in vitro. Plectin targeting shows potential as a strategy to inhibit tumor invasiveness as shown in cultured tumor spheroids while oral administration of plecstatin-1 to mice reduces tumor growth more efficiently in the invasive B16 melanoma than in the CT26 colon tumor model.

Using platinum(iv) prodrugs of clinically established platinum(ii) compounds is a strategy to overcome side effects and acquired resistances. We studied four oxaliplatin-derived platinum(iv) complexes with varying axial ligands in various in vitro and in vivo settings. The ability to interfere with DNA (pUC19) in the presence and absence of a reducing agent (ascorbic acid) was investigated in cell-free experiments. Cytotoxicity was compared under normoxic and hypoxic conditions in monolayer cultures and multicellular spheroids of colon carcinoma cell lines. Effects on the cell cycle were investigated by flow cytometry, and the capacity of inducing apoptosis was confirmed by flow cytometry and Western blotting. The anti-cancer activity of one complex was studied in vivo in immunodeficient and immunocompetent mice, and the platinum levels in various organs and the tumor after treatment were quantified. The results demonstrate that modification of the axial ligands can improve the cytotoxic potency. The complexes are able to interfere with plasmid DNA, which is enhanced by co-incubation with a reducing agent, and cause cell cycle perturbations. At higher concentrations, they induce apoptosis, but generate only low levels of reactive oxygen species. Two of the complexes increase the life span of leukemia (L1210) bearing mice, and one showed effects similar to oxaliplatin in a CT26 solid tumor model, despite the low platinum levels in the tumor. As in the case of oxaliplatin, activity in the latter model depends on an intact immune system. These findings show new perspectives for the development of platinum(iv) prodrugs of the anticancer agent oxaliplatin, combining bioreductive properties and immunogenic aspects.

Treatment with plecstatin-1 resulted in disruption of the cytoskeleton and phosphorylation of the stress marker eIF2α, and induction of an immunogenic cell death signature, including calreticulin, high mobility group protein B and extracellular ATP.

We have synthesized and structurally characterized three tetra-(ptolyl)antimony(III)-containing heteropolytungstates, [{(p-tolyl)Sb III } 4 (A-α-XW 9 O 34 ) 2 ] n− [X = P V (1-P), As V (1-As), or Ge IV (1-Ge)], in aqueous solution using conventional, one-pot procedures. The polyanions 1-P, 1-As, and 1-Ge were fully characterized in the solid state and in solution and were shown to be soluble and stable in aqueous medium at pH 7. Biological studies demonstrated that all three polyanions possess significant antibacterial and antitumor activities. The minimum inhibitory concentrations of 1-P, 1-As, and 1-Ge were determined against four kinds of bacteria, including the two pathogenic bacteria strains, Vibrio parahaemolyticus and Vibrio vulnificus. The three novel polyanions also showed high cytotoxic potency in the human cell lines A549 (non-small cell lung cancer), CH1/ PA-1 (ovarian teratocarcinoma), and SW480 (colon carcinoma).

Three copper(II) complexes of a series of bidentate dipyridylmethane ligands, as well as their structurally related platinum(II) analogues, have been synthesised and fully characterised to evaluate their coordination chemistry and antiproliferative properties. New crystal structures of the complexes L3CuCl2, L2PtCl2 and L3PtCl2, where L2, L3 have one and two methyl substituents on the bridgehead carbon atom between the coordinated pyridine ligands, respectively, were obtained. The in vitro cytotoxicity of the free ligands and their corresponding platinum and copper complexes was evaluated in the cisplatin‐sensitive ovarian teratocarcinoma cell line CH1/PA1, as well as in rather cisplatin‐insensitive colon (SW480) and lung (A549) carcinoma cells, using the MTT assay. All six complexes showed higher cytotoxicity than the ligands L1–L3 alone, giving IC50 values in the low micromolar range.