Anticancer Tungstenocenes with a Diverse Set of (O,O-), (O,S-) and (O,N-) Chelates-A Detailed Biological Study Using an Improved Evaluation via 3D Spheroid Models.

The synthesis, characterization and biological activity of tungstenocenes with varying biologically active (O,O-), (S,O-) and (N,O-) chelates are described. Complexes were characterized by 1H and 13C NMR, elemental analysis, ESI-mass spectrometry, FT-IR spectroscopy and X-ray diffraction analysis. The aqueous stability was studied by UV/Vis spectroscopy and the WIV to WV process by cyclic voltammetry. The cytotoxicity was determined by the MTT assay in A549, CH1/PA-1 and SW480 cancer cells as well as in IMR-90 human fibroblasts. Extensive biological evaluation was performed in three other human cancer cell lines (HCT116, HT29 and MCF-7) in monolayer and multicellular tumor spheroid cultures to better understand the mode of action. Lead compounds showed promising in vitro anticancer activity in all cancer cell lines. Further studies yielded important insights into apoptosis induction, ROS generation, different patterns in metal distribution (detected by LA-ICP-TOF-MS), changes in KI67 (proliferation marker) expression and DNA interactions. The results based on qualitative and quantitative research designs show that complexes containing (S,O-) chelates are more active than their (O,O-) and (N,O-) counterparts. The most striking results in spheroid models are the high antiproliferative capacity and the different distribution pattern of two complexes differing only in a W-S or W-O bond.

The First Anticancer Tris(pyrazolyl)borate Molybdenum(IV) Complexes: Tested in Vitro and in Vivo-A Comparison of O,O-, S,O-, and N,N-Chelate Effects.

The synthesis, characterization and biological activity of molybdenum(IV) complexes containing Trofimenko's scorpionato ligand, hydrotris(3-isopropylpyrazolyl)borate (TpiPr ), in addition to varying biologically active as well as other conventional ligands is described. Ligands employed include (O,O-) (S,O-) (N,N-) donors that have been successfully coordinated to the molybdenum center by means of oxygen-atom transfer (OAT) reactions from the known MoVI starting material, TpiPr MoO2 Cl. The synthesized complexes were characterized by standard analytical methods and where possible by X-ray diffraction analysis. The aqueous stability of the compounds was studied by means of UV/Vis spectroscopy and the impact of the attached ligand scaffolds on the oxidation potentials (MoIV to MoV ) was studied by cyclic voltammetry. Utilizing polyvinylpyrrolidone (PVP) as a solubilizing agent, adequate aqueous solubility for biological tests was obtained. Anticancer activity tests and preliminary mode of action studies have been performed in vitro and in vivo.