BIOLOGICAL PROPERTIES OF 2 GOLD(III) COMPLEXES - AUCL3(HPM) AND AUCL2(PM)

The reactivity in solution of two recently characterized gold(III) com plexes, AuCl3(Hpm) and AuCl2(pm), has been investigated in view of the ir potential use as anticancer agents. In water, both compounds underg o relatively fast hydrolysis of the bound chlorides without loss of th e heterocycle ligand; the process is much faster within a physiologica l buffer. When the two gold(lll) complexes react with proteins like al bumin or transferrin, reduction of gold(III) to gold(I) and / or hydro lysis is observed. On the other hand both complexes bind rapidly and t ightly to either polynucleotides or calf thymus DNA, with gold remaini ng in the +3 oxidation state. Circular dichroism investigations reveal a large perturbation of DNA conformation upon gold(III) binding; pref erential binding to GC sequences is shown. Cytotoxicity studies on a n umber of tumor cell lines demonstrate a good activity of these gold(II I) complexes compared to cisplatin. However, quick hydrolysis and / or reduction of these compounds under physiological conditions may repre sent a severe limitation to their use. (C) 1997 Elsevier Science Inc.