Auranofin and its Analogues Show Potent Antimicrobial Activity Covering Multiresistant Pathogens: Structure-Activity Relationships

Due to the so called “antibiotic resistance crisis” new antibacterial agents are urgently sought to treat multi-resistant pathogens. A group of gold- or silver-based complexes, of general formula M(PEt3)X (with M=Au or Ag, and X=Cl, Br or I), alongside with three complexes bearing a positive or negative charge, i.e. [Au(PEt3)2]Cl, K[Au(CN)2] and [Ag(PEt3)2]NO3, have been prepared and comparatively tested with Auranofin (AF) toward a representative panel of pathogens including Gram-positive, Gram-negative and Candida strains. Interestingly, all tested gold and silver complexes are active on Gram-positive strains, with the gold complexes presenting a greater efficacy. The effects of the gold compounds are potentiated to a larger extent than silver compounds when tested in combination with a permeabilizing agent. A few relevant structure-activity relationships emerge from comparative analysis of the obtained antibacterial profiles shedding new light on the underlying molecular mechanisms.