Monofunctional platinum(II) compounds and nucleolar stress: is phenanthriplatin unique?
| Autor: | Emily C. Sutton, Christopher H. Hendon, Matthew V. Yglesias, Min Chieh Yang, Victoria J. DeRose, Christine E. McDevitt, Austin M. Mroz |
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| Rok vydání: | 2019 |
| Předmět: |
Organoplatinum Compounds
DNA damage Nucleolus chemistry.chemical_element Antineoplastic Agents Biochemistry Article Inorganic Chemistry chemistry.chemical_compound Structure-Activity Relationship medicine Structure–activity relationship Humans Cytotoxicity Platinum Cisplatin Nucleophosmin Chemistry Phenanthriplatin Nuclear Proteins Biological Transport Phenanthridines Oxaliplatin A549 Cells Biophysics medicine.drug DNA Damage |
| Zdroj: | J Biol Inorg Chem |
| ISSN: | 1432-1327 |
| Popis: | Platinum anticancer therapeutics are widely used in a variety of chemotherapy regimens. Recent work has revealed that the cytotoxicity of oxaliplatin and phenanthriplatin is through induction of ribosome biogenesis stress pathways, differentiating them from cisplatin and other compounds that mainly work through DNA damage response mechanisms. In order to probe the structure-activity relationships in phenanthriplatin’s ability to cause nucleolar stress, a series of monofunctional platinum(II) compounds differing in ring number, size and orientation were tested by nucleophosmin (NPM1) relocalization assays using A549 cells. Phenanthriplatin was found to be unique among these compounds in inducing NPM1 relocalization. To decipher underlying reasons, computational predictions of steric bulk, platinum(II)-compound surface length and hydrophobicity were performed for all compounds. Of the monofunctional platinum(II) compounds tested, phenanthriplatin has the highest calculated hydrophobicity and volume but does not exhibit the largest distance from platinum(II) to the surface. Thus, spatial orientation and/or hydrophobicity caused by the presence of a third aromatic ring may be significant factors in the ability of phenanthriplatin to cause nucleolar stress. |
| Databáze: | OpenAIRE |
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