Redox-cycling and intercalating properties of novel mixed copper(II) complexes with non-steroidal anti-inflammatory drugs tolfenamic, mefenamic and flufenamic acids and phenanthroline functionality: Structure, SOD-mimetic activity, interaction with albumin, DNA damage study and anticancer activity
| Autor: | Klaudia Jomová, Lucia Kucerova, Zuzana Kozovska, Peter Lauro, Simona Rajcaniova, Marian Valko, Lenka Hudecova, Ján Moncol, Lubomir Svorc, Miriama Simunkova, Ibrahim M. Alhazza, Saleh Alwasel, Martin Danko |
|---|---|
| Rok vydání: | 2018 |
| Předmět: |
DNA damage
Radical Phenanthroline Intercalation (chemistry) Antineoplastic Agents Serum Albumin Human 010402 general chemistry 01 natural sciences Biochemistry Medicinal chemistry Inorganic Chemistry chemistry.chemical_compound Mefenamic Acid Biomimetic Materials Coordination Complexes Cell Line Tumor Escherichia coli Humans ortho-Aminobenzoates Hydrogen peroxide Gel electrophoresis chemistry.chemical_classification Reactive oxygen species 010405 organic chemistry Superoxide Dismutase Anti-Inflammatory Agents Non-Steroidal Biological activity DNA Intercalating Agents 0104 chemical sciences Flufenamic Acid Fenamates chemistry Reactive Oxygen Species Oxidation-Reduction Copper DNA Damage Phenanthrolines |
| Zdroj: | Journal of inorganic biochemistry. 194 |
| ISSN: | 1873-3344 |
| Popis: | Copper(II) complexes containing non-steroidal anti-inflammatory drugs (NSAIDs) have been the subject of many research papers and reviews. Here we report the synthesis, spectroscopic study and biological activity of novel mixed copper(II) complexes with NSAIDs: tolfenamic (tolf), mefenamic (mef) and flufenamic (fluf) acids and phenanthroline (phen): [Cu(tolf-O,O′)2(phen)] (1), [Cu(mef-O,O′)2(phen)] (2), [Cu(fluf-O,O′)2(phen)] (3). Complexes were characterized by X-ray analysis and EPR spectroscopy. Complexes 1–3 are monomeric, six-coordinate and crystallize in a monoclinic space group. Interaction of Cu(II) complexes with DNA was studied by means of absorption titrations, viscosity measurements and gel electrophoresis. The relative ability of the complexes to cleave DNA even in the absence of hydrogen peroxide is in the order 3 > 2 > 1. Application of the reactive oxygen species (ROS) scavengers, L-histidine, DMSO and SOD confirmed that singlet oxygen, hydroxyl radicals (Fenton reaction) and superoxide radical were formed, respectively. Thus, in addition to mechanism of intercalation, redox-cycling mechanism which in turn lead to the formation of ROS contribute to DNA damage. Cu(II) complexes exhibit excellent SOD-mimetic activity in the order 3~1 > 2. The fluorescence spectroscopy revealed that albumin may act as a targeted drug delivery vehicle for Cu(II) complexes (K~106). The anticancer activities of complexes 1–3 were investigated using an MTS assay (reduction of the tetrazolium compound) against three cancer cell lines (HT-29 human colon adenocarcinoma, HeLa and T-47D breast cancer cells) and mesenchymal stromal cells (MSC). The most promising compound, from the viewpoint of its NSAID biological activity is 3, due to the presence of the three fluorine atoms participating in the formation of weak hydrogen-bonds at the DNA surface. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect