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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
- 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.
- Subjects :
- 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
Subjects
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⟩