Metal compounds are gaining attention as agents to address antibiotic resistance, although development faces high costs and risks of failure. Strategies like drug repurposing, combination and bioconjugation may simplify clinical translation.

Auranofin (AF) is a gold-based compound with a well-known pharmacological and toxicological profile, currently used in the treatment of some severe forms of rheumatoid arthritis. Over the last twenty years, AF has also been repurposed as antiviral, antitumor, and antibacterial drug. In this review we focused on the antibacterial properties of AF, specifically researching the minimal inhibitory concentrations (MIC) of AF in both mono- and diderm bacteria reported so far in literature. AF proves to be highly effective against monoderm bacteria, while diderm are far less susceptible, probably due to the outer membrane barrier. We also reported the current mechanistic hypotheses concerning the antimicrobial properties of AF, although a conclusive description of its antibacterial mode of action is not yet available. Even if its mechanism of action has not been fully elucidated yet and further studies are required to optimize its delivery strategy, AF deserves additional investigation because of its unique mode of action and high efficacy against a wide range of pathogens, which could lead to potential applications in fighting antimicrobial resistance and improving therapeutic outcomes in infectious diseases.

Trypanothione reductase from Trypanosoma brucei (TbTR) is a key enzyme of the parasite responsible for human African trypanosomiasis. TbTR catalyzes the reduction of trypanothione, an antioxidant dithiol that protects trypanosomatid parasites from oxidative stress induced by the mammalian host as a defense system. TbTR is considered an attractive target for the development of novel anti‐parasitic drugs because it is essential for parasite survival and has no close homologues in humans. Previous studies have shown that metal compounds can act as potent inhibitors of trypanothione reductase and of related enzymes and may be considered for disease treatment. To better understand the molecular basis of such inhibition, we report the study of the interactions of a small group of metal compounds with TbTR, analyzed by ESI MS measurements. This technique allows direct visualization of the enzyme in solution and the detection and characterization of the metal binding process. Accordingly, TbTR was reacted with a panel of metal compounds including thimerosal, auranofin, its halogen analogues, and bismuth acetate. ESI MS results provide a detailed description of the interactions taking place for each metal compound tested. The implications of these results for the development of novel metal‐based compounds as potential anti‐trypanosomal agents are discussed.