title: Structural and solution chemistry, antiproliferative effects, and DNA and protein binding properties of a series of dinuclear gold(III) compounds with bipyridyl ligands.
abstract: A series of six dinuclear gold(III) oxo complexes with bipyridyl ligands, of general formula [Au2(N,N)2(mu-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 approximately 10-30 microM), the sixth one (Auoxo6), turned out to be approximately 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.
authors.affiliation: Department of Chemistry, University of Florence, Florence, Italy.
authors.forename: Angela
authors.initials: A
authors.lastname: Casini
authors.forename: Maria Agostina
authors.initials: MA
authors.lastname: Cinellu
authors.forename: Giovanni
authors.initials: G
authors.lastname: Minghetti
authors.forename: Chiara
authors.initials: C
authors.lastname: Gabbiani
authors.forename: Marcella
authors.initials: M
authors.lastname: Coronnello
authors.forename: Enrico
authors.initials: E
authors.lastname: Mini
authors.forename: Luigi
authors.initials: L
authors.lastname: Messori
mesh_terms: D015082:2,2'-Dipyridyl / Q000737:chemistry*; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D045744:Cell Line, Tumor; D004247:DNA / Q000737:chemistry*; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D008024:Ligands; D050607:Organogold Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D011485:Protein Binding; D012996:Solutions; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D008024:Ligands; D050607:Organogold Compounds; D012996:Solutions; D015082:2,2'-Dipyridyl; D004247:DNA; C427203:calf thymus DNA