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

Serratrice, Maria, Edafe, Fabio, Mendes, Filipa, Scopelliti, Rosario, Zakeeruddin, Shaik Mohammed, Graetzel, Michael, Santos, Isabel, Cinellu, Maria Agostina and Casini, Angela ORCID: https://orcid.org/0000-0003-1599-9542 2012. Cytotoxic gold compounds: synthesis, biological characterization and investigation of their inhibition properties of the zinc finger protein PARP-1. Dalton Transactions 41 (11) , pp. 3287-3293. 10.1039/C2DT11913G

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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.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Chemistry
Subjects:	Q Science > QD Chemistry
Publisher:	Royal Society of Chemistry
Date of Acceptance:	8 December 2011
Last Modified:	31 Oct 2022 08:57
URI:	https://orca.cardiff.ac.uk/id/eprint/79324

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