Structural characterization and biological evaluation of a clioquinol–ruthenium complex with copper-independent antileukaemic activity
| Autor: | Jakob Kljun, Iztok Turel, Irena Mlinarič-Raščan, Matija Uršič, Izidor Sosič, Stanislav Gobec, Martina Gobec |
|---|---|
| Rok vydání: | 2014 |
| Předmět: |
Proteasome Endopeptidase Complex
Programmed cell death Stereochemistry Base pair chemistry.chemical_element Antineoplastic Agents Apoptosis Ruthenium Inorganic Chemistry Inhibitory Concentration 50 Jurkat Cells chemistry.chemical_compound Cell Line Tumor medicine Humans Dimethyl Sulfoxide Cell Proliferation Leukemia Dose-Response Relationship Drug Clioquinol Cell Cycle NF-kappa B Oxyquinoline Hedgehog signaling pathway Mechanism of action chemistry Drug Design MCF-7 Cells Biophysics Drug Screening Assays Antitumor medicine.symptom Copper Derivative (chemistry) medicine.drug |
| Zdroj: | Dalton Trans.. 43:9045-9051 |
| ISSN: | 1477-9234 1477-9226 |
| Popis: | In this study, we present the synthesis, biological characterization, and first crystal structure of an organometallic-clioquinol complex. Combining ruthenium with the established apoptotic agent and 8-hydroxyquinoline derivative, clioquinol, resulted in a complex that induces caspase-dependent cell death in leukaemia cells. This activity is copper independent and is improved compared to the parent compound, clioquinol. The study of the mode of action reveals that this clioquinol-ruthenium complex does not intercalate between DNA base pairs. Additionally, this clioquinol-ruthenium complex shows proteasome-independent inhibition of the NFκB signalling pathway, with no effects on cell-cycle distribution. These data suggest a mechanism of action that involves a target profile that is different from that for clioquinol alone. |
| Databáze: | OpenAIRE |
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