期刊
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
卷 179, 期 -, 页码 325-334出版社
ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER
DOI: 10.1016/j.ejmech.2019.06.065
关键词
Organometallic anticancer agents; Palladacyclopentadienyl compounds; Ovarian cancer; N-Heterocyclic carbenes; DNA damage
资金
- AIRC (My First AIRC) [15639]
New palladacyclopentadienyl complexes with bis-N-heterocyclic carbenes as spectator ligands have been synthesized and exhaustively characterized. The crystal structure of complex la has been also determined by X-ray diffraction analysis. Their in vitro cytotoxicity and that of other palladacyclopentadienyl derivatives coordinating different ancillary ligands has been determined against different cancer cell lines. Many complexes have shown an antiproliferative activity toward tumor cells often definitely better than cisplatin, whereas they have resulted practically inactive against the non-cancer MRC-5 cell line. The mechanism of action of bis-NHC derivative la, particularly active against ovarian cancer cell lines was studied in depth. Through a longitudinally analysis, it is shown that compound la induces apoptosis via DNA damage and release of cytochrome C. We propose compound la as a powerful and specific drug for the therapy of a deadly disease such as high grade serous ovarian cancer. (C) 2019 Elsevier Masson SAS. All rights reserved.
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