Ruthenium–arene complexes with NSAIDs: synthesis, characterization and bioactivity
| Autor: | Sanja Grgurić-Šipka, Milena Krstić, Athanasios N. Papadopoulos, Jelena Poljarević, Marijana Kajzerberger, Sandra Aranđelović, Siniša Radulović, George Psomas, Chrisoula Kakoulidou, Ana Tadić |
|---|---|
| Rok vydání: | 2018 |
| Předmět: |
DNA-BINDING
010402 general chemistry 01 natural sciences NICKEL(II) COMPLEXES Catalysis chemistry.chemical_compound Materials Chemistry medicine CRYSTAL-STRUCTURE MTT assay ZINC-COMPLEXES BIOLOGICAL EVALUATION Cytotoxicity Cisplatin chemistry.chemical_classification Reactive oxygen species 010405 organic chemistry COPPER(II) COMPLEXES MEFENAMIC-ACID NONSTEROIDAL ANTIINFLAMMATORY DRUGS IN-VITRO General Chemistry Molecular biology 3. Good health 0104 chemical sciences Mechanism of action chemistry Apoptosis Cell culture medicine.symptom Ethidium bromide ANTIOXIDANT ACTIVITY medicine.drug |
| Zdroj: | New Journal of Chemistry |
| ISSN: | 1369-9261 1144-0546 |
| DOI: | 10.1039/c7nj04416j |
| Popis: | 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] |
| Databáze: | OpenAIRE |
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