Antitumor trans-N-Heterocyclic Carbene-Amine-Pt(II) Complexes: Synthesis of Dinuclear Species and Exploratory Investigations of DNA Binding and Cytotoxicity Mechanisms
| Autor: | Angela Marinetti, Laure Eloy, Pascal Retailleau, Evelyne Ségal-Bendirdjian, Thierry Cresteil, Sophie Bombard, Lina Saker, Joël Poupon, Hélène Jullien, Mélanie Chtchigrovsky |
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| Přispěvatelé: | Institut de Chimie des Substances Naturelles (ICSN), Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC), Laboratoire de toxicologie, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Lariboisière-Fernand-Widal [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Laboratoire de Chimie et de Biochimie Pharmacologiques et Toxicologiques (LCBPT - UMR 8601), Université Paris Descartes - Paris 5 (UPD5)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) - Hôpital Lariboisière, Université Paris Descartes - Paris 5 (UPD5) - Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Lariboisière, Université Paris Descartes - Paris 5 (UPD5)-Centre National de la Recherche Scientifique (CNRS) |
| Jazyk: | angličtina |
| Rok vydání: | 2013 |
| Předmět: |
Organoplatinum Compounds
Stereochemistry Antineoplastic Agents Apoptosis DNA Fragmentation Diamines 010402 general chemistry 01 natural sciences Inhibitory Concentration 50 chemistry.chemical_compound Cell Line Tumor Diamine Drug Discovery medicine Humans Bifunctional Cytotoxicity Cell Proliferation Cisplatin 010405 organic chemistry Cell growth [CHIM.ORGA]Chemical Sciences/Organic chemistry Cell Cycle Apoptosis Inducing Factor DNA Cell cycle [CHIM.ORGA] Chemical Sciences/Organic chemistry 0104 chemical sciences chemistry Molecular Medicine Amine gas treating Carbene medicine.drug |
| Zdroj: | Journal of Medicinal Chemistry Journal of Medicinal Chemistry, American Chemical Society, 2013, 56 (5), pp.2074-86. ⟨10.1021/jm301780s⟩ Journal of Medicinal Chemistry, American Chemical Society, 2013, 56 (5), pp.2074-86. 〈10.1021/jm301780s〉 |
| ISSN: | 0022-2623 1520-4804 |
| DOI: | 10.1021/jm301780s⟩ |
| Popis: | International audience; A series of bimetallic [(NHC)PtX2]2(diamine) complexes have been prepared as a new chemotype for potential anticancer agents. These complexes display an uncommon set of structural features as far as they combine two bifunctional, trans-configured platinum centers. They display cytotoxic activities in the micromolar range on many cancerous cell lines and do not cross-react with cisplatin in A2780/DDP cell lines. They bind slowly to double-stranded DNAs, giving monoadducts as the major products. Pathways for cellular toxicity have been investigated for both mono- and bimetallic trans-(NHC)PtX2(amine) complexes. It has been highlighted that, unlike cisplatin, these complexes do not induce cell cycle arrest. They trigger apoptosis in A2780 cells by a pathway involving translocation of apoptosis-inducing factor and caspase 12 to the nucleus. Moreover, bimetallic complexes may induce necrosis. |
| Databáze: | OpenAIRE |
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