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Structural and solution chemistry, antiproliferative effects, and DNA and protein binding properties of a series of dinuclear gold(III) compounds with bipyridyl ligands

Casini, Angela, Cinellu, Maria Agostina, Minghetti, Giovanni, Gabbiani, Chiara, Coronnello, Marcella, Mini, Enrico and Messori, Luigi 2006. Structural and solution chemistry, antiproliferative effects, and DNA and protein binding properties of a series of dinuclear gold(III) compounds with bipyridyl ligands. Journal of Medicinal Chemistry 49 (18) , pp. 5524-5531. 10.1021/jm060436a

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Abstract

A series of six dinuclear gold(III) oxo complexes with bipyridyl ligands, of general formula [Au2(N,N)2(μ-O)2][PF6]2 (Auoxo1−Auoxo6) [where N,N = 2,2‘-bipyridine (1), 4,4‘-di-tert-butyl- (2), 6-methyl- (3), 6-neopentyl- (4), 6-(2,6-dimethylphenyl)- (5), 6,6‘-dimethyl-2,2‘-bipyridine (6)], were investigated as potential cytotoxic and anticancer agents, and their antiproliferative properties were evaluated in vitro toward the reference A2780 human ovarian carcinoma cell line. While five compounds manifested moderate cytotoxic properties (with IC50 ≈ 10−30 μM), the sixth one (Auoxo6), turned out to be ∼5−15 times more active against both cell lines and will merit further pharmacological studies. The interactions of Auoxo1 and Auoxo6 with a few model proteins (serum albumin, cytochrome c, ubiquitin) and with calf thymus DNA were analyzed in detail by various spectroscopic methods. Both tested compounds manifested a high and peculiar reactivity toward the mentioned model proteins; specific differences were detected in their reactivity with DNA. The mechanistic implications of these results are discussed.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Chemistry
Subjects: Q Science > QD Chemistry
Publisher: American Chemical Society
Last Modified: 04 Jun 2017 08:30
URI: http://orca.cf.ac.uk/id/eprint/79381

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