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Antitumor trans-N-Heterocyclic Carbene-Amine-Pt(II) Complexes: Synthesis of Dinuclear Species and Exploratory Investigations of DNA Binding and Cytotoxicity Mechanisms

Antitumor trans-N-Heterocyclic Carbene-Amine-Pt(II) Complexes: Synthesis of Dinuclear Species and Exploratory Investigations of DNA Binding and Cytotoxicity Mechanisms

Authors :
Angela Marinetti
Laure Eloy
Pascal Retailleau
Evelyne Ségal-Bendirdjian
Thierry Cresteil
Sophie Bombard
Lina Saker
Joël Poupon
Hélène Jullien
Mélanie Chtchigrovsky
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)
Source :
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〉
Publication Year :
2013
Publisher :
HAL CCSD, 2013.

Abstract

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.

Details

Language :
English
ISSN :
00222623 and 15204804
Database :
OpenAIRE
Journal :
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〉
Accession number :
edsair.doi.dedup.....f703354eefc5a3d49850ffbc29af6caf
Full Text :
https://doi.org/10.1021/jm301780s⟩