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

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 anticancer 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(lll) 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. (C) 1997 Elsevier Science Inc.