1. Experimental and theoretical investigations of cyclometalated ruthenium(ii) complex containing CCC-pincer and anti-inflammatory drugs as ligands: synthesis, characterization, inhibition of cyclooxygenase and in vitro cytotoxicity activities in various cancer cell lines.
- Author
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Tabrizi L, Olasunkanmi LO, and Fadare OA
- Subjects
- Adamantane analogs & derivatives, Adamantane chemistry, Antineoplastic Agents chemistry, Antineoplastic Agents pharmacology, Cell Line, Tumor, Cell Survival drug effects, Coordination Complexes chemistry, Coordination Complexes pharmacology, Cyclooxygenase Inhibitors chemistry, Cyclooxygenase Inhibitors pharmacology, Drug Stability, HEK293 Cells, Humans, Ibuprofen chemistry, Ligands, MCF-7 Cells, Molecular Docking Simulation, Molecular Structure, Naproxen chemistry, Organophosphorus Compounds chemistry, Reactive Oxygen Species metabolism, Antineoplastic Agents chemical synthesis, Coordination Complexes chemical synthesis, Cyclooxygenase Inhibitors chemical synthesis, Ruthenium chemistry
- Abstract
The new cyclometalated ruthenium(ii) complex, [Ru(CCC-Nap)(Ibu)(PTA)] was designed and synthesized using ibuprofen (Ibu), 1,3,5-triaza-7-phosphaadamantane (PTA) and CCC-pincer containing naproxen moiety (CCC-Nap) as ligands. The compounds were fully characterized by elemental analysis, FT-IR, multinuclear (1H, 13C, and 31P) NMR spectroscopy, and electrospray ionization mass spectrometry. The cytotoxicity of the newly synthesized Ru(ii) complex was found to be low, and the complex was about twice as active as cisplatin with IC50 values in the range of 0.9-1.32 μM for both MCF-7 and MDA-MB-231 cell lines. Cyclooxygenase (COX) inhibition studies revealed that the Ru(ii) complex displayed strong interactions with COX-2, about 16 and 5 times more than free Ibu and CCC-Nap ligands, respectively. The Ru(ii) complex improved the production of reactive oxygen species (ROS) by 10.7 fold compared to the control (H2O2 as a positive control) in MCF-7 cells. Quantum chemical calculations gave more insights into the geometry and electronic properties of the novel Ru(ii) complex, while molecular docking provided theoretical information on the interactions of Ru(ii) complex with human cyclooxygenase-2 (COX-2) and the results were compared with those of the interactions of the free ligands with COX-2.
- Published
- 2019
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