Aurocyanide, dicyano-aurate (I), a pharmacologically active metabolite of medicinal gold complexes

Abstract

The aurocyanide anion, Au(CN) 2- , is a human metabolite of several anti-rheumatic gold complexes containing monovalent gold (I) bound to a sulphur ligand. This article reviews some of the chemical and pharmacological properties of this intriguing metabolite, and reports its anti-arthritic and anti-inflammatory activity in rats. Au(CN) 2- is generated from the therapeutic gold complexes by small amounts of hydrogen cyanide, HCN, produced from thiocyanate, SCN-, by myeloperoxidase (MPO) an enzyme in neutrophils which normally produces hypochlorite, OCl-. Thus, Au(CN) 2- is formed at sites of inflammation where activated neutrophils are present. This includes atherosclerotic lesions as well as inflamed joints. MPO also oxidises Au(CN) 2- to Au(III) complexes such as Au(CN) 4- . Au(CN) 2- is normally a very stable monovalent gold complex. In a biological context, only low concentrations are ever present at both extracellular and intracellular sites. However, Au(CN) 2- produced locally may facilitate the cellular uptake and hence the therapeutic and toxic effects of gold drugs. Au(CN) 2- may also be involved in a redox cycle where Au(CN) 2- is oxidised to Au(CN) 4- which is, in turn, reduced back to Au(CN) 2- by endogenous thiols. There are still many questions to be resolved concerning Au(CN) 2- including its intrinsic toxicity and the extent to which it may contribute to the overall anti-arthritic activities of the gold-thiolates from which it is formed in vivo.