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

• Published in: Journal of inorganic biochemistry Vol. 66; no. 2; pp. 103 - 109
• Main Authors: Calamai, P, Carotti, S, Guerri, A, Messori, L, Mini, E, Orioli, P, Speroni, G P
• Format: Journal Article
• Language: English
• Published: United States 01.05.1997
• Subjects: 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
• ISSN: 0162-0134
• DOI: 10.1016/S0162-0134(96)00190-0

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.