Exploring the Molecular Mechanisms Underlying the in vitro Anticancer Effects of Multitarget‐Directed Hydrazone Ruthenium(II)–Arene Complexes
| العنوان: | Exploring the Molecular Mechanisms Underlying the in vitro Anticancer Effects of Multitarget‐Directed Hydrazone Ruthenium(II)–Arene Complexes |
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| المؤلفون: | Massimiliano Cuccioloni, Laura Bonfili, Mauro Angeletti, Riccardo Petrelli, Loredana Cappellacci, Anna Maria Eleuteri, Massimo Nabissi, Fabio Marchetti, Riccardo Pettinari, Valentina Cecarini |
| المصدر: | ChemMedChem. 15:105-113 |
| بيانات النشر: | Wiley, 2019. |
| سنة النشر: | 2019 |
| مصطلحات موضوعية: | Cell Membrane Permeability, Stereochemistry, media_common.quotation_subject, Serum albumin, Hydrazone, chemistry.chemical_element, Antineoplastic Agents, Apoptosis, 01 natural sciences, Biochemistry, Ruthenium, Cell membrane, chemistry.chemical_compound, Coordination Complexes, Cell Line, Tumor, Drug Discovery, medicine, Humans, General Pharmacology, Toxicology and Pharmaceutics, Internalization, Cytotoxicity, media_common, Pharmacology, chemistry.chemical_classification, Binding Sites, biology, 010405 organic chemistry, Organic Chemistry, Hydrazones, Cell Cycle Checkpoints, DNA, In vitro, 0104 chemical sciences, Molecular Docking Simulation, Kinetics, 010404 medicinal & biomolecular chemistry, medicine.anatomical_structure, chemistry, biology.protein, Nucleic Acid Conformation, Molecular Medicine, Hydroxymethylglutaryl CoA Reductases, Cyclin-Dependent Kinase Inhibitor p27, Protein Binding |
| الوصف: | The molecular targets and the modes of action behind the cytotoxicity of two structurally established N,O- or N,N-hydrazone ruthenium(II)-arene complexes were explored in human breast adenocarcinoma cells (MCF-7) and paralleled in non-cancerous and cisplatin-resistant counterparts (MCF-10A and MCF-7CR respectively). Both complexes, [Ru(hmb)(L1)Cl] (1, L1=4-((2-(2,4-dinitrophenyl)hydrazono)(phenyl)methyl)-3-methyl-1-phenyl-1H-pyrazol-5-olate) and [Ru(cym)(L2)Cl] (2, L2=1-((3-methyl-5-oxo-1-phenyl-1H-pyrazol-4(5H)-ylidene)(phenyl)methyl)-2-(pyridin-2-yl)hydrazin-1-ide), reversibly interact with moderate-to-high affinity with a number of molecular targets in cell-free assays, namely serum albumin, DNA, the 20S proteasome and hydroxymethylglutaryl-CoA reductase. Most interestingly, only 2 readily crosses the cell membrane and preserves its binding/modulatory ability toward the targets of interest upon rapid cellular internalization. The resulting action at multiple levels of the cancer cascade is likely the cause for the selective sensitization of tumour cells to p27-mediated apoptotic death, and for the ability of 2 to overcome the drug resistance problem. |
| تدمد: | 1860-7187 1860-7179 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::6998f8b0f4699db4e3fa2f6f17dbac7aTest https://doi.org/10.1002/cmdc.201900551Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....6998f8b0f4699db4e3fa2f6f17dbac7a |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 18607187 18607179 |
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