- Structural and solution chemistry, antiproliferative effects, and serum albumin binding of three pseudohalide derivatives of auranofin
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Three pseudohalide analogues of the established gold drug auranofin (AF hereafter), of general formula Au(PEt3)X, i.e. Au(PEt3)CN, Au(PEt3)SCN and Au(PEt3)N3 (respectively denoted as AFCN, AFSCN and AFN3), were prepared and characterized. The crystal structure was solved for Au(PEt3)SCN highlighting the classical linear geometry of the 2-coordinate gold(I) center. The solution behaviour of the compounds was then comparatively analysed through 31PNMR providing evidence for an acceptable stability under physiological-like conditions. Afterward, the reaction of these gold compounds with bovine serum albumin (BSA) and consequent adduct formation was investigated by 31PNMR. For all the studied gold compounds, the [Au(PEt3)]+ moiety was identified as the reactive species in metal/protein adducts formation. The cytotoxic effects of the complexes were subsequently measured in comparison to AF against a representative colorectal cancer cell line and found to be still relevant and roughly similar in the three cases though far weaker than those of AF. These results show that the nature of the anionic ligand can modulate importantly the pharmacological action of the gold-triethylphosphine moiety, affecting the cytotoxic potency. These aspects may be further explored to improve the pharmacological profiles of this family of metal complexes.
- Cirri, Damiano,Fabbrini, Maria Giulia,Massai, Lara,Pillozzi, Serena,Guerri, Annalisa,Menconi, Alessio,Messori, Luigi,Marzo, Tiziano,Pratesi, Alessandro
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- Synthesis and spectroscopic characterization of (triethylphosphine)gold(I) complexes AuX(PEt3) (X = Cl, Br, CN, SCN), [AuL(PEt3)+] (L = SMe2, SC(NH2)2, H2O), and (μ-S)[Au(PEt3)]2
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Neutral complexes of the type AuX(PEt3) (X = Br, CN, SCN) were prepared and characterized by infrared and Raman spectroscopy, with the major emphasis on the assignment of the gold-ligand vibrations and discerning the mode of bonding for the ambidentate ligands. The photosensitive cationic complexes [(Au(SMe2)(PEt3)]PF6 and {Au[SC(NH2)2](PEt3)}(Cl in addition to [Au(OH2)(PEt3)]NO3 and (μ-S)[(PEt3)Au]2 were also prepared and characterized by infrared and NMR spectroscopy. In both cases in which the ambidentate ligands SCN- and SC(NH2)2 were complexed with Au(I), the sulfur atom coordinates to the metal, providing evidence for a symbiotic relationship in these complexes.
- El-Etri,Scovell
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p. 480 - 484
(2008/10/08)
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