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

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

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Edafe, Fabio Mendes, Filipa Casini, Angela Scopelliti, Rosario Grätzel, Michael Santos, Isabel Cinellu, Maria Agostina Zakeeruddin, Shaik Mohammed Serratrice, Maria
Description	Author Affiliation: Serratrice M ( Department of Chemistry, University of Sassari, Sassari, Italy.)
Abstract	The new gold(III) complexes: $[Au\{2-(2′-pyridyl)imidazolate\}Cl_{2}]$ and $[Au\{2,6-bis(2′-benzimidazolate)pyridine\}(OCOCH_{3})]$ and the mono- and binuclear gold(I) complexes: $[Au\{2-(2′-pyridyl)imidazole\}(PPh_{3})](PF_{6}),$ [Au(2-phenylimidazolate)(DAPTA)] (DAPTA = 3,7-diacetyl-1,3,7-triaza-5-phosphabicyclo[3.3.1]nonane), $[(PPh_{3}Au)_{2}(2-R-imidazolate)](PF_{6})$ (R = $2-C_{5}H_{4}N,$ Ph) have been synthesized and characterized. The structure of the $[(PPh_{3}Au)_{2}\{2-(2′-pyridyl)imidazolate)](PF_{6})$ 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 $[(PPh_{3}Au)_{2}\{2-(2′-pyridyl)imidazolate)](PF_{6})$ 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.
ISSN	14779226
Issue Number	11
Volume Number	41
e-ISSN	13645447
Journal	Dalton Trans.
Language	English
Publisher	Royal Society of Chemistry
Publisher Date	2012-03-21
Publisher Place	Great Britain (UK)
Access Restriction	Subscribed
Subject Keyword	Cytotoxins Chemical Synthesis Organogold Compounds Toxicity Poly(ADP-ribose) Polymerase Inhibitors Breast Neoplasms Drug Therapy Pathology Cell Line, Tumor Cell Proliferation Drug Effects Female Humans Ovarian Neoplasms Journal Article Research Support, Non-U.S. Gov't Chemistry
Content Type	Text
Resource Type	Article
Subject	Inorganic Chemistry

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Development of new poly(ADP-ribose) polymerase (PARP) inhibitors in ovarian cancer: Quo Vadis?

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The Inhibition and Treatment of Breast Cancer with Poly (ADP-ribose) Polymerase (PARP-1) Inhibitors

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

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