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Issue 11, 2012
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Cytotoxic gold compounds: synthesis, biological characterization and investigation of their inhibition properties of the zinc finger protein PARP-1

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Abstract

The new gold(III) complexes: [Au{2-(2′-pyridyl)imidazolate}Cl2] and [Au{2,6-bis(2′-benzimidazolate)pyridine}(OCOCH3)] and the mono- and binuclear gold(I) complexes: [Au{2-(2′-pyridyl)imidazole}(PPh3)](PF6), [Au(2-phenylimidazolate)(DAPTA)] (DAPTA = 3,7-diacetyl-1,3,7-triaza-5-phosphabicyclo[3.3.1]nonane), [(PPh3Au)2(2-R-imidazolate)](PF6) (R = 2-C5H4N, Ph) have been synthesized and characterized. The structure of the [(PPh3Au)2{2-(2′-pyridyl)imidazolate)](PF6) complex was also characterized by X-ray crystallography. The antiproliferative properties of the complexes were assayed against human ovarian carcinoma cell lines, either sensitive (A2780) or resistant to cisplatin (A2780cisR), human mammary carcinoma cells (MCF7) and non-tumorigenic human kidney (HEK293) cells. Most of the studied compounds showed important cytotoxic effects. Interestingly, the compounds containing the 2-(2′-pyridyl)imidazolate ligand showed selectivity towards cancer cells with respect to the non-tumorigenic ones, with the dinuclear compound [(PPh3Au)2{2-(2′-pyridyl)imidazolate)](PF6) being the most active. Some compounds were also screened for their inhibitory effect of the zinc-finger protein PARP-1, essential for DNA repair and relevant to the mechanisms of cancer cell resistance to cisplatin. Interaction studies of the compounds with the model protein ubiquitin were undertaken by electrospray ionization mass spectrometry (ESI MS). The results are discussed in relation to the putative mechanisms of action of the cytotoxic gold compounds.

Graphical abstract: Cytotoxic gold compounds: synthesis, biological characterization and investigation of their inhibition properties of the zinc finger protein PARP-1

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Publication details

The article was received on 12 Oct 2011, accepted on 08 Dec 2011 and first published on 31 Jan 2012


Article type: Paper
DOI: 10.1039/C2DT11913G
Citation: Dalton Trans., 2012,41, 3287-3293
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    Cytotoxic gold compounds: synthesis, biological characterization and investigation of their inhibition properties of the zinc finger protein PARP-1

    M. Serratrice, F. Edafe, F. Mendes, R. Scopelliti, S. M. Zakeeruddin, M. Grätzel, I. Santos, M. A. Cinellu and A. Casini, Dalton Trans., 2012, 41, 3287
    DOI: 10.1039/C2DT11913G

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