Metal compounds as antimicrobial agents: 'smart' approaches for discovering new effective treatments.

Due to their considerable chemical diversity, metal compounds are attracting increasing and renewed attention from the scientific and medical communities as potential antimicrobial agents to combat the growing problem of antibiotic resistance. The development of metal compounds as antimicrobial agents typically follows classical drug discovery procedures and suffers from the same problems; indeed, these procedures can be very expensive and time-consuming, and carry an intrinsically high risk of failure. Here, we show how some established drug discovery approaches can be conveniently and successfully applied to antimicrobial metal compounds to provide some shortcuts for faster clinical translation of new treatments.

Novel NMR-Based Approach to Reveal the 'Metabolic Fingerprint' of Cytotoxic Gold Drugs in Cancer Cells.

A combination of pathway enrichment and metabolite clustering analysis is used to interpret untargeted H NMR metabolomics data, enabling a biochemically informative comparison of the effects induced by a panel of known cytotoxic gold(I) and gold(III) compounds in A2780 ovarian cancer cells. The identification of the most dysregulated pathways for the major classes of compounds highlights specific chemical features that lead to common biological effects. The proposed approach may have broader applicability to the screening of metal-based drug candidate libraries, which is always complicated by their multitarget nature, and support the comprehensive interpretation of their metabolic actions.

Deciphering the role of neutral diruthenium complexes in protein binding.

The charge of paddlewheel diruthenium complexes has a major role in defining their interaction with proteins: negatively charged complexes bind proteins non-covalently, while cationic complexes form adducts where the Ru core binds to Asp side chains at the equatorial sites, or to the main chain carbonyl groups or the side chains of His, Arg or Lys residues at the axial sites. Here we study the interactions of the neutral compound [Ru(D-p-FPhF)(OCCH)(OCO)]·3HO (D-p-FPhF = N,N'-bis(4-fluorophenyl)formamidinate), a very rare example of a paddlewheel diruthenium compound with three different equatorial ligands, with the model protein bovine pancreatic ribonuclease (RNase A) by means of UV-visible absorption spectroscopy, circular dichroism (CD), electrospray ionization mass spectrometry (ESI-MS) and X-ray crystallography. It is the first attempt to investigate the binding of a neutral diruthenium compound to a protein.

Non-Medical Applications of Inorganic Medicines. A Switch Based on Mechanistic Knowledge.

Metals have been used in medicine for centuries. However, it was not until much later that the effects of inorganic drugs could be rationalized from a mechanistic point of view. Today, thanks to the technologies available, this approach has been functionally developed and implemented.

The Many Lives of Auranofin: How an Old Anti-Rheumatic Agent May Become a Promising Antimicrobial Drug.

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.