Auranofin and its Analogues Show Potent Antimicrobial Activity against Multidrug-Resistant Pathogens: Structure-Activity Relationships

Due to the so-called "antibiotic resistance crisis" new antibacterial agents are urgently sought to treat multidrug-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-[Au(PEt₃ )₂ ]Cl, K[Au(CN)₂ ] and [Ag(PEt₃ )₂ ]NO₃ -were prepared and comparatively tested with auranofin on a representative panel of pathogens including Gram-positive, Gram-negative and Candida strains. Interestingly, all the gold and silver complexes tested were active on Gram-positive strains, with the gold complexes having greater efficacy. The effects of the gold compounds were potentiated to a larger extent than silver compounds when tested in combination with a permeabilizing agent. A number of relevant structure-activity relationships emerged from the comparative analysis of the observed antibacterial profiles, shedding new light on the underlying molecular mechanisms of the action of these compounds.