title: Superior cytotoxicity of hydrophylic gold carboxylato complexes over hydrophylic silver carboxylates.
abstract: BACKGROUND
  The water-soluble ionic gold(I) complex [Au(PPh(2)CH(2)CH(2)PPh(2))(2)]Cl possesses at least ten times stronger antineoplastic activity than the water-soluble neutral silver(I) carboxylates [AgO(2)C(CH(2)OCH(2))(n)H], 1, (n=1), 2 (n=2), or 3 (n=3) even though Au(I) and Ag(I) are isoelectronic d(10) metals lying one above the other in the periodic table of the elements. In this study we determined the cytotoxicity of the stable water-soluble gold(I) carboxylates [(Ph(3)P)AuO(2)C(CH(2)OCH(2))(n)H], 4 (n=1), 5 (n=2) and 6 (n=3) to compare the intrinsic antineoplastic activity of gold(I) and silver(I) under conditions where different complex charges do not influence the result.
  
  
  METHODS
  The cytotoxicity of carboxylato gold complexes 4-6 towards the HeLa (human cervix epithelioid) cancer cell line ATCC CCL-2, resting lymphocytes and phytohaemagglutinin(PHA)-stimulated lymphocytes were determined. Cell survival was measured by means of the colorimetric 3-(4,5-dimethylthiazol-2-yl)-diphenyltetrazolium bromide (MTT) assay.
  
  
  RESULTS
  The IC(50) values of 4-6 from six experiments causing 50% cell growth inhibition were essentially constant; values ranged between 0.50 and 0.82 μmol dm(-3). Drug activity was thus independent of the carboxylato ligand chain length. Metal complexes 4-6 were at least one order of magnitude more cytotoxic towards the HeLa cancer cell line than the silver carboxylates 1-3 and were almost as cytotoxic as [Au(PPh(2)CH(2)CH(2)PPh(2))(2)]Cl and cisplatin [(H(3)N)(2)PtCl(2)]. Complexes 4-6 were also 2-5 times more toxic against PHA-stimulated lymphocyte cultures than to HeLa cancer cell.
  
  
  CONCLUSIONS
  Unlike for the silver complexes 1-3, no meaningful drug activity-structural relationship exists for the gold(I) d(10) carboxylates 4-6. Gold(I) complexes in neutral and charged form are intrinsically more cytotoxic than silver(I) against the HeLa cancer cell line.
authors: Department of Chemistry, University of the Free State, Bloemfontein 9300, Republic of South Africa.
authors: Ernst H G
authors: EH
authors: Langner
authors: Jannie C
authors: JC
authors: Swarts
authors: André
authors: A
authors: Tuchscherer
authors: Heinrich
authors: H
authors: Lang
authors: Gisela K
authors: GK
authors: Joone
authors: Constance E J
authors: CE
authors: VAN Rensburg
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology*; D002264:Carboxylic Acids / Q000737:chemistry / Q000494:pharmacology*; D048708:Cell Growth Processes / Q000187:drug effects; D056831:Coordination Complexes / Q000737:chemistry / Q000494:pharmacology*; D004354:Drug Screening Assays, Antitumor; D006046:Gold / Q000737:chemistry*; D006367:HeLa Cells; D006801:Humans; D012834:Silver / Q000737:chemistry*; D012995:Solubility; D014867:Water / Q000737:chemistry
chemical_list: D000970:Antineoplastic Agents; D002264:Carboxylic Acids; D056831:Coordination Complexes; D014867:Water; D012834:Silver; D006046:Gold