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Mechanistic studies on two dinuclear organogold(III) compounds showing appreciable antiproliferative properties and a high redox stability

Gabbiani, Chiara and Casini, Angela and Kelter, Gerhard and Cocco, Fabio and Cinellu, Maria Agostina and Fiebig, Heinz Herbert and Messori, Luigi (2011) Mechanistic studies on two dinuclear organogold(III) compounds showing appreciable antiproliferative properties and a high redox stability. Metallomics, Vol. 3 (12), p. 1318-1323. eISSN 1756-591X. Article.

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DOI: 10.1039/C1MT00113B

Abstract

Two dinuclear oxo-bridged organogold(III) compounds, namely [(N,N,C)2Au2(μ-O)][PF6]2 (with N,N,CH = 6-(1-methylbenzyl)-2,2′-bipyridine, Au2O1; or 6-(1,1-dimethylbenzyl)-2,2′-bipyridine, Au2O2), were previously prepared and characterised. Their solution chemistry under physiological-like conditions has been investigated here as well as their in vitro antiproliferative properties. Notably, these compounds reveal a marked redox stability even in the presence of effective biological reductants such as ascorbic acid and glutathione. The two dinuclear gold(III) compounds were evaluated for cytotoxic actions against a representative panel of 12 human tumor cell lines, in comparison to respective mononuclear parent compounds [(N,N,C)AuOH][PF6], and appreciable biological activity could be highlighted. The reactions of Au2O1 and Au2O2 with a few model proteins were studied and the ability to form metallodrug–protein adducts monitored through ESI MS methods. Typical adducts were identified where the protein is associated to monometallic gold fragments; in these adducts gold remains in the oxidation state +3 and conserves its organic ligand. A direct comparison of the biological profiles of these binuclear organogold(III) compounds with those previously reported for a series of dinuclear oxo-bridged complexes [(N,N)2Au2(μ-O)2][PF6]2 (N,N = 6(6′)-substituted 2,2′-bipyridines) named Auoxo's was carried out. It emerges that the greater cytotoxicity of the latter is mainly due to the greater oxidising power of their gold(III) centres and to propensity to generate gold(I) species; in contrast, the here described bimetallic organogold(III) complexes manifest a far higher redox stability in the biological milieu coupled to lower, but still significant, antiproliferative properties. Different molecular mechanisms are thus hypothesised for these two classes of dinuclear gold(III) agents.

Item Type:Article
ID Code:7274
Status:Published
Refereed:Yes
Uncontrolled Keywords:Mechanistic studies, antiproliferative properties, organogold derivatives
Subjects:Area 03 - Scienze chimiche > CHIM/03 Chimica generale e inorganica
Divisions:001 Università di Sassari > 01 Dipartimenti > Chimica
Publisher:Royal Society of Chemistry
eISSN:1756-591X
Additional Information:This article is part of the collection: Third International Symposium on Metallomics, Münster, Germany 2011.
Deposited On:21 Mar 2012 16:56

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