The biological activity of auranofin: implications for novel treatment of diseases

Abstract

More than 30 years ago, auranofin was developed for the treatment of rheumatoid arthritis as a substitution for the injectable gold compounds aurothiomalate and aurothioglucose. Both the ease of oral administration over intramuscular injections and more potent anti-inflammatory effects in vitro made auranofin seem like an excellent substitute for the traditional injectable gold compounds. Despite efficacy in the treatment of both rheumatoid arthritis and psoriasis, currently, auranofin is seldom used as a treatment for patients with rheumatoid arthritis as more novel anti-rheumatic medications have become available. Despite the decline in its clinical applications, research on auranofin has continued as it shows promise in the treatment of several different diseases. In recent years, advances in technology have allowed researchers to use molecular techniques to identify novel mechanisms of action of auranofin. Additionally, researchers are discovering potential new applications of auranofin. Dual inhibition of inflammatory pathways and thiol redox enzymes by auranofin makes it a new candidate for cancer therapy and treating microbial infections. This review will summarize recently obtained data on the mechanisms of action of auranofin, and potential new applications of auranofin in the treatment of various diseases, including several types of leukaemia, carcinomas, and parasitic, bacterial, and viral infections.

Evidence that the antiproliferative effects of auranofin in Saccharomyces cerevisiae arise from inhibition of mitochondrial respiration

“…In addition, four clinical trials were started against various cancer types and are still ongoing. A recent review by Madeira et al (Madeira et al, 2012) summarizes the "state of art" on the medical applications of AF.…”

In vitro antibacterial and time-kill evaluation of phosphanegold(I) dithiocarbamates, R3PAu[S2CN(iPr)CH2CH2OH] for R = Ph, Cy and Et, against a broad range of Gram-positive and Gram-negative bacteria

“…Despite this, antibacterial studies on gold compounds are still relatively limited [10][11][12][13][14][15] and more often than not focussing on gold(I) rather on gold(III) compounds. The primary focus of these studies is usually upon the inherent interest in the chemistry and consequently the accompanying antimicrobial work is often limited to the measurement of minimum inhibitory concentration (MIC) and sometimes minimum bactericidal concentration (MBC).…”

Metal-based glycoconjugates and their potential in targeted anticancer chemotherapy

“…Together with its antiinflammatory activity, the complex [(2,3,4,6-tetra-O-acetyl-1-thio-β-d-glucopyranosato-S) (triethylphosphino)]gold(I) (auranofin) showed promising anticancer activity in vitro and, as such, was extensively studied [103]. In fact, it proved cytotoxic toward several human tumor cell lines, including cisplatin-sensitive and -resistant ovarian cells [104], multiple myeloma [105] and leukemia [106] cells.…”

“…As to its mechanism of action, the antiarthritic activity seems to arise from the inhibition of enzymes such as cyclooxygenases [103], whereas the inactivation of the seleno-enzyme thioredoxinreductase is likely to account for its anticancer properties [104]. Nevertheless, the actual mechanism of transport and cellular internalization of auranofin is still unclear.…”