Biological properties of two gold(III) complexes: AuCl3(Hpm) and AuCl2(pm)

J Inorg Biochem. 1997 May 1;66(2):103-9. doi: 10.1016/s0162-0134(96)00190-0.

Abstract

The reactivity in solution of two recently characterized gold(III) complexes, AuCl3(Hpm) and AuCl2(pm), has been investigated in view of their potential use as anti-cancer agents. In water, both compounds undergo relatively fast hydrolysis of the bound chlorides without loss of the heterocycle ligand; the process is much faster within a physiological buffer. When the two gold(III) complexes react with proteins like albumin or transferrin, reduction of gold(III) to gold(I) and/or hydrolysis is observed. On the other hand, both complexes bind rapidly and tightly to either polynucleotides or calf thymus DNA, with gold remaining in the +3 oxidation state. Circular dichroism investigations reveal a large perturbation of DNA conformation upon gold(III) binding; preferential binding to GC sequences is shown. Cytotoxicity studies on a number of tumor cell lines demonstrate a good activity of these gold(III) complexes compared to cisplatin. However, quick hydrolysis and/or reduction of these compounds under physiological conditions may represent a severe limitation to their use.

MeSH terms

  • Antineoplastic Agents / toxicity*
  • Cell Survival / drug effects
  • Chlorides / toxicity
  • Cisplatin / toxicity
  • DNA / chemistry*
  • DNA / drug effects
  • Gold Compounds / chemistry
  • Gold Compounds / pharmacology*
  • Gold Compounds / toxicity
  • Humans
  • Nucleic Acid Conformation / drug effects
  • Polydeoxyribonucleotides / chemistry*
  • Polydeoxyribonucleotides / metabolism
  • Serum Albumin / chemistry*
  • Serum Albumin / metabolism
  • Solutions
  • Spectrophotometry
  • Transferrin / chemistry*
  • Transferrin / metabolism
  • Tumor Cells, Cultured

Substances

  • Antineoplastic Agents
  • Chlorides
  • Gold Compounds
  • Polydeoxyribonucleotides
  • Serum Albumin
  • Solutions
  • Transferrin
  • gold chloride
  • gold tetrachloride, acid
  • DNA
  • Cisplatin