Thiolato gold(I) complexes containing water-soluble phosphane ligands: a characterization of their chemical and biological properties.

A series of thiolate gold(I) derivatives bearing water soluble phosphanes--namely sodium triphenylphosphane monosulfonate (TPPMS), sodium triphenylphosphane trisulfonate (TPPTS), 1,3,5-triaza-7-phosphaadamantane (PTA) and 3,7-diacetyl-1,3,7-triaza-5-phosphabicyclo[3.3.1]nonane (DAPTA)--is reported and the compounds studied for their luminescence properties in the solid state. Two of these derivatives, [Au(SMe(2)pyrim)(PTA)] and [Au(SBenzoxazole)(DAPTA)], are also structurally characterized by X-ray diffraction analysis. Strong antiproliferative effects are observed for most of the compounds in the human ovarian carcinoma cell lines (A2780/S) and its cisplatin-resistant variant (A2780/R), which depend on both the type of thiolate and phosphane ligands. ICP-MS studies were also performed to evaluate the influence of the gold uptake on the cytotoxic potency of the compounds.

[1]  A. Casini,et al.  Metal-based inhibition of poly(ADP-ribose) polymerase--the guardian angel of DNA. , 2011, Journal of medicinal chemistry.

[2]  K. P. Bhabak,et al.  Bioinorganic and medicinal chemistry: aspects of gold(I)-protein complexes. , 2011, Dalton transactions.

[3]  R. Alberto,et al.  Performance of a 99mTc-labelled 1-thio-&bgr;-D-glucose 2,3,4,6-tetra-acetate analogue in the detection of infections and tumours in mice: a comparison with [18F]FDG , 2010, Nuclear medicine communications.

[4]  A. Modesti,et al.  Exploring the biochemical mechanisms of cytotoxic gold compounds: a proteomic study , 2010, JBIC Journal of Biological Inorganic Chemistry.

[5]  A. Casini,et al.  Anticancer Therapeutics That Target Selenoenzymes: Synthesis, Characterization, in vitro Cytotoxicity, and Thioredoxin Reductase Inhibition of a Series of Gold(I) Complexes Containing Hydrophilic Phosphine Ligands , 2010, ChemMedChem.

[6]  E. Björn,et al.  Evaluation of cell lysis methods for platinum metallomic studies of human malignant cells. , 2010, Analytical biochemistry.

[7]  Q. Dou,et al.  Inhibition of tumor proteasome activity by gold–dithiocarbamato complexes via both redox‐dependent and ‐independent processes , 2010, Journal of cellular biochemistry.

[8]  L. Ronconi,et al.  The Midas touch in cancer chemotherapy: from platinum- to gold-dithiocarbamato complexes. , 2009, Dalton transactions.

[9]  I. Ubarretxena-Belandia,et al.  Water Soluble Phosphane-Gold(I) Complexes. Applications as Recyclable Catalysts in a Three-component Coupling Reaction and as Antimicrobial and Anticancer Agents. , 2009, European journal of inorganic chemistry.

[10]  C. Cannon,et al.  The medicinal applications of imidazolium carbene-metal complexes. , 2009, Chemical reviews.

[11]  A. Casini,et al.  Chemistry, antiproliferative properties, tumor selectivity, and molecular mechanisms of novel gold(III) compounds for cancer treatment: a systematic study , 2009, JBIC Journal of Biological Inorganic Chemistry.

[12]  C. Che,et al.  The anti-cancer properties of gold(III) compounds with dianionic porphyrin and tetradentate ligands , 2009 .

[13]  I. Ott.  On the medicinal chemistry of gold complexes as anticancer drugs , 2009 .

[14]  E. Tiekink,et al.  Luminescence properties of phosphinegold(I) halides and thiolates , 2009 .

[15]  A. Casini,et al.  Thioredoxin reductase: A target for gold compounds acting as potential anticancer drugs , 2009 .

[16]  B. Keppler,et al.  Carbohydrate-metal complexes and their potential as anticancer agents. , 2008, Current medicinal chemistry.

[17]  M. Laguna,et al.  Synthesis, characterization, and in vitro cytotoxicity of some gold(I) and trans platinum(II) thionate complexes containing water-soluble PTA and DAPTA ligands. X-ray crystal structures of [Au(SC4H3N2)(PTA)], trans-[Pt(SC4H3N2)2(PTA)2], trans-[Pt(SC5H4N)2(PTA)2], and trans-[Pt(SC5H4N)2(DAPTA)2]. , 2008, Inorganic chemistry.

[18]  A. Casini,et al.  Gold(III) compounds as anticancer agents: relevance of gold-protein interactions for their mechanism of action. , 2008, Journal of inorganic biochemistry.

[19]  A. Pombeiro,et al.  Water-soluble and stable dinitrogen phosphine complexes trans-[ReCl(N2)(PTA-H)n(PTA)4-n]n+ (n = 0-4), the first with 1,3,5-triaza-7-phosphaadamantane. , 2008, Dalton transactions.

[20]  W. Kean,et al.  Clinical pharmacology of gold , 2008, Inflammopharmacology.

[21]  E. Tiekink.  Anti-cancer potential of gold complexes , 2008, Inflammopharmacology.

[22]  S. Berners‐Price,et al.  Targeting the mitochondrial cell death pathway with gold compounds , 2007 .

[23]  E. Tiekink,et al.  Gold(I) and Palladium(II) Thiolato Complexes Containing Water-Soluble Phosphane Ligands , 2007 .

[24]  L. Jones,et al.  Gold compounds as efficient co-catalysts in palladium-catalysed alkynylation , 2007 .

[25]  L. Jones,et al.  Homogenous catalysis with gold : Efficient hydration of phenylacetylene in aqueous media , 2007 .

[26]  J. Kovács,et al.  (META-SULFONATOPHENYL)DIPHENYLPHOSPHINE, SODIUM SALT AND ITS COMPLEXES WITH RHODIUM(I), RUTHENIUM(II), IRIDIUM(I) , 2007 .

[27]  D. Darensbourg,et al.  1,3,5‐Triaz‐7‐Phosphatricyclo[3.3.1.13,7]Decane and Derivatives , 2007 .

[28]  James L. Hickey,et al.  Cationic, linear Au(I) N-heterocyclic carbene complexes: synthesis, structure and anti-mitochondrial activity. , 2006, Dalton transactions.

[29]  E. Tiekink,et al.  Water-soluble and water-stable organometallic gold(II) complexes , 2006 .

[30]  M. Laguna,et al.  Organometallic gold(I) and gold(III) complexes containing 1,3,5-triaza-7-phosphaadamantane (TPA): Examples of water-soluble organometallic gold compounds , 2006 .

[31]  I. Kostova.  Gold coordination complexes as anticancer agents. , 2006, Anti-cancer agents in medicinal chemistry.

[32]  B. Frost,et al.  Effect of pH on the Biphasic Catalytic Hydrogenation of Benzylidene Acetone Using CpRu(PTA)2H , 2005 .

[33]  C. Supuran,et al.  Carbonic anhydrase inhibitors: synthesis and topical intraocular pressure lowering effects of fluorine-containing inhibitors devoid of enhanced reactivity. , 2004, Journal of medicinal chemistry.

[34]  D. Darensbourg,et al.  A New Water-Soluble Phosphine Derived from 1,3,5-Triaza-7-phosphaadamantane (PTA),† 3,7-Diacetyl-1,3,7-triaza-5-phosphabicyclo[3.3.1]nonane. Structural, Bonding, and Solubility Properties , 2004 .

[35]  Maria Cristina Burla,et al.  SIR2002: the program , 2003 .

[36]  Anthony L. Spek,et al.  Journal of , 1993 .

[37]  S. Berners‐Price,et al.  Mechanisms of cytotoxicity and antitumor activity of gold(I) phosphine complexes: the possible role of mitochondria , 2002 .

[38]  E. Tiekink.  Gold derivatives for the treatment of cancer. , 2002, Critical reviews in oncology/hematology.

[39]  C. Shaw.  Gold-Based Therapeutic Agents , 1999 .

[40]  D. Darensbourg,et al.  1,3,5-TRIAZA-7-PHOSPHATRICYCLO3.3.1.13,7DECANE AND DERIVATIVES , 1998 .

[41]  Z. Assefa,et al.  Bis(1,3,5-triaza-7-phosphaadamantane-P)-gold(I) chloride , 1996 .

[42]  R. Staples,et al.  Luminescence Studies of Gold(I) Thiolate Complexes , 1995 .

[43]  Z. Assefa,et al.  Structures and Spectroscopic Properties of Gold(I) Complexes of 1,3,5-Triaza-7-phosphaadamantane (TPA). 2. Multiple-State Emission from (TPA)AuX (X = Cl, Br, I) Complexes , 1995 .

[44]  P. van der Sluis,et al.  BYPASS: an effective method for the refinement of crystal structures containing disordered solvent regions , 1990 .