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Heterobimetallic platinum(II) complexes with increased cytotoxicity against ovarian cancer cell lines
Authors: Melounková Lucie | Syková Miriam | Jirásko Robert | Jambor Roman | Havelek Radim | Peterova Eva | Honzíček Jan | Vinklárek Jaromír
Year: 2021
Type of publication: článek v odborném periodiku
Name of source: New Journal of Chemistry
Publisher name: Royal Society of Chemistry
Place: Cambridge
Page from-to: 19506-19514
Titles:
Language Name Abstract Keywords
cze Heterobimetalické platnaté komplexy se zvýšenou cytotoxicitou vůči nádorovým buňkám Byly připraveny dvě série heterobimetalických sloučenin vycházejících z platnatého komplexu obsahujícího aminofosfinový ligand. Zahrnují neutrální Pt-Sn komplexy a iontové Pt-Ag komplexy. In vitro studie na iontových sloučeninách prokázala vysoký cytotoxický efekt na nádorových buňkách včetně buněčné linie rezistentní vůči cisplatině. Pt; fosfin; cytotoxicita
eng Heterobimetallic platinum(II) complexes with increased cytotoxicity against ovarian cancer cell lines Two series of heterobimetallic compounds were prepared from the starting complex [cis-L2PtCl2] containing an aminophosphine ligand (L = 2,6-iPr(2)-C6H3-NHPPh2). They include neutral Pt-Sn complexes [cis-L2PtX(SnCl3)] (X = Cl, SnCl3) and ionic Pt-Ag complexes [cis-L2PtCl2Ag]X (X = OTf, PF6). The in vitro WST-1 assays of the ionic complexes revealed a high cytotoxic effect on ovarian cancer cells, including the cisplatin resistant cell line A2780cis, while the sensitivity to the non-cancer cell line MRC-5 stays very low. The mechanism of the cytotoxic effect was studied in detail on one representative. It revealed the up-regulation of the apoptotic proteins p38 and BAX, activation of caspase 9 and initiation of cell apoptosis. Here, cell death is accompanied by an increased amount of p21 protein and increased activity of the check point kinases, which result in the G2 arrest. Sensitivity to cisplatin resistant cells, high selectivity to cancer cells and activity at a low dosage are the advantages of the Pt-Ag compounds presented here. Pt; phosphine; ligands; binding; dna; 8-thiotheophylline; chemistry; design

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