title: Structural and solution chemistry, protein binding and antiproliferative profiles of gold(I)/(III) complexes bearing the saccharinato ligand.
abstract: A series of new gold(I) and gold(III) complexes based on the saccharinate (sac) ligand, namely M[Au(sac)(2)] (with M being Na(+), K(+) or NH(4)(+)), [(PTA)Au(sac)], K[Au(sac)(3)Cl] and Na[Au(sac)(4)], were synthesized and characterized, and some aspects of their biological profile investigated. Spectrophotometric analysis revealed that these gold compounds, upon dissolution in aqueous media, at physiological pH, manifest a rather favourable balance between stability and reactivity. Their reactions with the model proteins cytochrome c and lysozyme were monitored by mass spectrometry to predict their likely interactions with protein targets. In the case of disaccharinato gold(I) complexes, cytochrome c adducts bearing four coordinated gold(I) ions were preferentially formed in high yield. In contrast, [(PTA)Au(sac)] (PTA=1,3,5-triaza-7-phosphaadamantane) turned out to be poorly effective, only producing a mono-metalated adduct in very low amount. In turn, the gold(III) saccharinate derivatives were less reactive than their gold(I) analogues: K[Au(sac)(3)Cl] and Na[Au(sac)(4)] caused moderate protein metalation, again with evidence of formation of tetragold adducts. Finally, the above mentioned gold compounds were challenged against the reference human tumor cell line A2780S and its cisplatin resistant subline A2780R and their respective cytotoxic profiles determined. [(PTA)Au(sac)] turned out to be highly cytotoxic whereas moderate cytotoxicities were observed for the gold(III) complexes and only modest activities for disaccharinato gold(I) complexes. The implications of these results are thoroughly discussed in the light of current knowledge on gold based drugs.
authors.affiliation: Department of Chemistry, University of Sassari, Sassari (SS), Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Maiore
authors.forename: Maria Agostina
authors.initials: MA
authors.lastname: Cinellu
authors.forename: Elena
authors.initials: E
authors.lastname: Michelucci
authors.forename: Gloriano
authors.initials: G
authors.lastname: Moneti
authors.forename: Stefania
authors.initials: S
authors.lastname: Nobili
authors.forename: Ida
authors.initials: I
authors.lastname: Landini
authors.forename: Enrico
authors.initials: E
authors.lastname: Mini
authors.forename: Annalisa
authors.initials: A
authors.lastname: Guerri
authors.forename: Chiara
authors.initials: C
authors.lastname: Gabbiani
authors.forename: Luigi
authors.initials: L
authors.lastname: Messori
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002945:Cisplatin / Q000737:chemistry / Q000494:pharmacology; D005260:Female; D006801:Humans; D020128:Inhibitory Concentration 50; D008024:Ligands; D050607:Organogold Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D010051:Ovarian Neoplasms / Q000378:metabolism / Q000473:pathology; D011485:Protein Binding / Q000187:drug effects; D012439:Saccharin / Q000031:analogs & derivatives / Q000737:chemistry*; D012996:Solutions / Q000737:chemistry; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D008024:Ligands; D050607:Organogold Compounds; D012996:Solutions; D012439:Saccharin; D002945:Cisplatin