New ruthenium(II) bipyridyl complex : synthesis, crystal structure and cytotoxicity

A new Ru(II) bipyridyl complex with O-4-hydrogenpyridine-2,4-dicarboxylate was synthesized and characterized by IR, NMR and mass spectrometry, X-ray diffraction analysis and elemental analysis. The electrochemical characteristics of the complex were investigated by cyclic voltammetry, revealing Ru(II)/Ru(III) electron transfer in the positive range of potentials. On the opposite potential side, multiple partially reversible peaks were dominant, representing subsequent reductions of the bulky bipyridyl moiety. The cytotoxic activity of the complex was tested in two human cancer cell lines: A549 (lung cancer) and K562 (leukemia) as well as non-tumor MRC-5 cells, by MTT assays. The IC50 values were >300 and 177.63+/-2.28 mu M for the A549 and K562 cells, respectively

Ruthenium-arene complexes with NSAIDs: synthesis, characterization and bioactivity

Two non-steroidal antiinflammatory drugs indomethacin and mefenamic acid were coordinated to Ru(II)-arenes to afford four new complexes. The cytotoxic activities of the ligands and ruthenium complexes were tested in three human cancer cell lines (K562, A549, MDA-MB-231) and non-tumour human fetal lung fibroblast cells (MRC-5) by MTT assay. Cytotoxicity studies revealed that indomethacin Ru(II)-arene complexes 1 and 3 displayed good cytotoxicity and apparent cytoselective profiles. The IC50 values obtained in leukemia K562 cells were comparable to those of cisplatin (10.3 mu M (CDDP), 11.9 mu M (1) and 13.2 mu M (3)). Flow cytometric analysis of 1 and 3 in triple-negative breast cancer MDA-MB-231 cells revealed an interesting mechanism of action. At IC50 concentrations, 1 and 3 arrested cell cycle progression in S phase and caused rapid accumulation of cells in sub-G1 phase (up to 48%), while Annexin V-FITC/PI staining showed simultaneous occurrence of apoptotic and necrotic cell populations at approximately similar levels of 20%. Measurement of reactive oxygen species (ROS) production by DCFH-DA staining confirmed the potential of 1 and 3 to increase ROS even more than cisplatin. The interaction of the complexes with serum albumins showed their potential ability to bind tightly and reversibly to albumins. The affinity of the complexes to calf-thymus DNA was investigated by UV-vis spectroscopy, viscosity measurements and fluorescence emission spectroscopy for competitive studies of the complexes with ethidium bromide, revealing that their interaction probably occurs via intercalation. Taken together, the results strongly suggest the potential of complexes 1 and 3 to alter cell cycle progression and cause DNA-damage by means of direct DNA-binding or indirectly by ROS production.Supplementary material: [http://cherry.chem.bg.ac.rs/handle/123456789/3038

The New EU Strategy for Central Asia: A Case for Cultural Diplomacy

<p>In June 2017, on the tenth anniversary of the first Central Asia Strategy, the Council of the European Union invited High Representative Federica Mogherini and the European Commission to draw a proposal for a new Strategy by late 2019. This decision provides an opportunity to review the shortcomings of the previous Strategy and to assess the evolving regional environment, in which Russia and China have consolidated their influence. </p> <p>By presenting current challenges in Central Asia, this policy brief argues that the new Strategy should enhance EU cultural diplomacy in the region. In line with the increased role of culture in European external action, EU cultural diplomacy should meet local citizenry’s aspirations and demands, and give Brussels a comparative advantage over other regional powers.</p