title: Antitumor trans-N-heterocyclic carbene-amine-Pt(II) complexes: synthesis of dinuclear species and exploratory investigations of DNA binding and cytotoxicity mechanisms.
abstract: 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.
authors: Institut de Chimie des Substances Naturelles, UPR CNRS 2301, 1 av. de la Terrasse, 91198 Gif-sur-Yvette, France.
authors: Mélanie
authors: M
authors: Chtchigrovsky
authors: Laure
authors: L
authors: Eloy
authors: Hélène
authors: H
authors: Jullien
authors: Lina
authors: L
authors: Saker
authors: Evelyne
authors: E
authors: Ségal-Bendirdjian
authors: Joel
authors: J
authors: Poupon
authors: Sophie
authors: S
authors: Bombard
authors: Thierry
authors: T
authors: Cresteil
authors: Pascal
authors: P
authors: Retailleau
authors: Angela
authors: A
authors: Marinetti
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D051033:Apoptosis Inducing Factor / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002945:Cisplatin / Q000494:pharmacology; D004247:DNA / Q000378:metabolism*; D053938:DNA Fragmentation; D003959:Diamines / Q000138:chemical synthesis / Q000494:pharmacology; D006801:Humans; D020128:Inhibitory Concentration 50; D009944:Organoplatinum Compounds / Q000138:chemical synthesis / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D051033:Apoptosis Inducing Factor; D003959:Diamines; D009944:Organoplatinum Compounds; D004247:DNA; D002945:Cisplatin