All this for .26 cents go figure ! 8. Conclusions
Ruthenium-based antimicrobial agents have a fairly complex mode of action involving multiple mechanisms acting in synergy. The knowledge gained so far in this area suggests that the activity of ruthenium compounds against microbial cells is based upon their ability to induce oxidative stress, interact with the genetic material, proteins, or other intracellular targets, and/or damage the cell membranes. The complex interplay between these modes of action is likely responsible for the activity of some ruthenium-based compounds against drug-resistant strains.
Generally, ruthenium complexes exert excellent activity against Gram-positive bacteria (e.g., S. aureus and MRSA) and, with some exceptions (see, for instance, the dinuclear polypyridylruthenium(II) complexes and ruthenium-based CORMs), display lower activity towards Gram-negative strains (e.g., E. coli and P. aeruginosa). With regard to their activity against Gram-negative bacteria, one can notice a trend towards higher efficacy against E. coli when compared with P. aeruginosa and K. pneumoniae. For most classes of compounds, activity towards both Gram-negative and Gram-positive strains has been correlated to the uptake of the complex into the cells.
Additionally, this work highlights recent advances in ruthenium-based compounds that are active against neglected tropical diseases caused by parasites, such as malaria, Chagas’ disease, and leishmaniasis. Notably, several complexes possess excellent activity, at submicromolar concentrations, results that raise awareness about the potential use of ruthenium compounds as effective antiparasitic agents. Moreover, the antiviral activity of ruthenium complexes, particularly the anti-HIV and anti-SARS-Cov-2 activities, has been reviewed herein. It is worth noting that BOLD-100 (formerly denoted KP1339) displays a broad antiviral mechanism of action and appears to remain active on all mutant strains of the SARS-Cov-2 virus.
In general terms, ruthenium complexes have been shown to display low levels of toxicity towards healthy eukaryotic cells in vitro and in vivo. This finding underlines the potential of these compounds for future clinical development, since selective toxicity against microbial over host cells in vitro and in vivo is imperative for a potential drug to advance in clinical trials. More in vivo studies are clearly needed in order to provide proof beyond a reasonable doubt that ruthenium complexes are strong candidates in the field of antimicrobial drug discovery.