Next Generation Gold Drugs and Probes: Chemistry and Biomedical Applications.

The gold drugs, gold sodium thiomalate (Myocrisin), aurothioglucose (Solganal), and the orally administered auranofin (Ridaura), are utilized in modern medicine for the treatment of inflammatory arthritis including rheumatoid and juvenile arthritis; however, new gold agents have been slow to enter the clinic. Repurposing of auranofin in different disease indications such as cancer, parasitic, and microbial infections in the clinic has provided impetus for the development of new gold complexes for biomedical applications based on unique mechanistic insights differentiated from auranofin. Various chemical methods for the preparation of physiologically stable gold complexes and associated mechanisms have been explored in biomedicine such as therapeutics or chemical probes. In this Review, we discuss the chemistry of next generation gold drugs, which encompasses oxidation states, geometry, ligands, coordination, and organometallic compounds for infectious diseases, cancer, inflammation, and as tools for chemical biology via gold-protein interactions. We will focus on the development of gold agents in biomedicine within the past decade. The Review provides readers with an accessible overview of the utility, development, and mechanism of action of gold-based small molecules to establish context and basis for the thriving resurgence of gold in medicine.