title: Cytotoxicity of ferrocenyl-ethynyl phosphine metal complexes of gold and platinum.
abstract: BACKGROUND
  Ferrocene derivatives may possess antineoplastic activity. Those with low ferrocenyl reduction potentials often have the highest anticancer activity, as cell components have to oxidise them to the active ferrocenium species before cytotoxicity can be recorded. Some gold(I) complexes also possess anticancer activity. This study examined the cytotoxicity of ferrocenyl-ethynyl and ruthenocenyl-ethynyl complexes of gold and platinum. The results were related to the ease of iron oxidation in the ferrocenyl fragment and compared with the cytotoxicity of cisplatin, [(H(3)N)(2)PtCl(2)] and [Au(PPh(2)CH(2)CH(2)PPh(2))(2)]Cl.
  
  
  METHODS
  Ferrocene-containing gold and platinum complexes of the type Fc-C≡C-PPh(2), 1, and Fc-C≡C-PPh(2)→M with Fc=ferrocenyl (Fe(II)(η(5)-C(5)H(5)) (η(5)-C(5)H(4))), Ph=phenyl (C(6)H(5)) and M=Au-Cl, 2, Au-C≡C-Fc, 3, or Au-C≡C-Rc, 4 (Rc=ruthenocenyl, (Ru(II)(η(5)-C(5)H(5)) (η(5)-C(5)H(4))) and the complex [(Fc-C≡C-PPh(2))(2)PtCl(2)], 5, were investigated. Cytotoxicity tests were determined on the HeLa (human cervix epitheloid) cancer cell line, ATCC CCL-2. Cell survival was measured by means of the colorometric 3-(4,5-dimethylthiazol-2-yl)-diphenyltetrazolium bromide assay.
  
  
  RESULTS
  The IC(50) values of compounds 1-4 from four experiments causing 50% cell growth inhibition, ranged between 4.6 and 27 μmol dm(-3). Drug activity was inversely proportional to the sum of all formal reduction potentials, E(o'), of the ferrocenyl groups of the Fc-C≡C-PPh(2) and Fc-C≡C-ligands coordinated to the gold centre. The Fc-C≡C-PPh(2)→Au-Cl complex, compound 2, was most cytotoxic with IC(50)=4.6 μmol dm(-3) , demonstrating the beneficial effect the Cl(-) ion has on the cytotoxicity of these neutral gold complexes. The platinum complex [(Fc-C≡C-PPh(2))(2)PtCl(2)], compound 5, resembling the structure of cisplatin, in principle should exhibit good cytotoxicity, but was not tested due to its total insolubility in any biocompatible medium.
authors.affiliation: Department of Chemistry, University of the Free State, Bloemfontein, 9300, Republic of South Africa.
authors.forename: Eleanor
authors.initials: E
authors.lastname: Fourie
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Erasmus
authors.forename: Jannie C
authors.initials: JC
authors.lastname: Swarts
authors.forename: Alexander
authors.initials: A
authors.lastname: Jakob
authors.forename: Heinrich
authors.initials: H
authors.lastname: Lang
authors.forename: Gisela K
authors.initials: GK
authors.lastname: Joone
authors.forename: Constance E J
authors.initials: CE
authors.lastname: VAN Rensburg
mesh_terms: D000480:Alkynes / Q000737:chemistry / Q000494:pharmacology*; D016923:Cell Death / Q000187:drug effects; D056831:Coordination Complexes / Q000737:chemistry / Q000494:pharmacology*; D004354:Drug Screening Assays, Antitumor; D005296:Ferrous Compounds / Q000737:chemistry / Q000494:pharmacology*; D006046:Gold / Q000737:chemistry / Q000494:pharmacology*; D006367:HeLa Cells; D006801:Humans; D020128:Inhibitory Concentration 50; D000075163:Metallocenes; D010084:Oxidation-Reduction / Q000187:drug effects; D010720:Phosphines / Q000737:chemistry / Q000494:pharmacology*; D010984:Platinum / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000480:Alkynes; D056831:Coordination Complexes; D005296:Ferrous Compounds; D000075163:Metallocenes; D010720:Phosphines; D010984:Platinum; D006046:Gold; C044646:phosphine; C004998:ferrocene