title: Insights into the reactivity of gold-dithiocarbamato anticancer agents toward model biomolecules by using multinuclear NMR spectroscopy.
abstract: Some gold(III)-dithiocarbamato derivatives of either single amino acids or oligopeptides have shown promise as potential anticancer agents, but their capability to interact with biologically relevant macromolecules is still poorly understood. We investigated the affinity of the representative complex [Au(III)Br2(dtc-Sar-OCH3)] (dtc: dithiocarbamate; Sar: sarcosine (N-methylglycine)) with selected model molecules for histidine-, methionine-, and cysteine-rich proteins (that is, 1-methylimidazole, dimethylsulfide, and N-acetyl-L-cysteine, respectively). In particular, detailed mono- and multinuclear NMR studies, in combination with multiple (13)C/(15)N enrichments, allowed interactions to be followed over time and indicated somewhat unexpected reaction pathways. Whereas dimethylsulfide proved to be unreactive, a sudden multistep redox reaction occurred in the presence of the other potential sulfur donor, N-acetyl-L-cysteine (confirmed if glutathione was used instead). On the other hand, 1-methylimidazole underwent an unprecedented acid-base reaction with the gold(III) complex, rather than the expected coordination to the metal center by replacing, for instance, a bromide. Our results are discussed herein and compared with the data available in the literature on related complexes; our findings confirm that the peculiar reactivity of gold(III)-dithiocarbamato complexes can lead to novel reaction pathways and, therefore, to new cytotoxic mechanisms in cancer cells.
authors.affiliation: Department of Chemical Sciences, University of Padova, Via F. Marzolo 1, Padova 35131 (Italy).
authors.forename: Giulia
authors.initials: G
authors.lastname: Boscutti
authors.forename: Luciano
authors.initials: L
authors.lastname: Marchiò
authors.forename: Luca
authors.initials: L
authors.lastname: Ronconi
authors.forename: Dolores
authors.initials: D
authors.lastname: Fregona
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology; D045744:Cell Line, Tumor; D056831:Coordination Complexes / Q000737:chemistry*; D006046:Gold / Q000737:chemistry*; D006801:Humans; D019906:Nuclear Magnetic Resonance, Biomolecular; D050607:Organogold Compounds / Q000737:chemistry* / Q000494:pharmacology; D013859:Thiocarbamates / Q000737:chemistry* / Q000494:pharmacology
chemical_list: D000970:Antineoplastic Agents; D056831:Coordination Complexes; D050607:Organogold Compounds; D013859:Thiocarbamates; D006046:Gold
keywords: NMR spectroscopy; antitumor agents; dithiocarbamates; gold