Auranofin and its Analogues Show Potent Antimicrobial Activity against Multidrug-Resistant Pathogens:
Tiziano Marzo1,2, Damiano Cirri1, Simona Pollini3,4
1Laboratory of Metals in Medicine (MetMed), Department of Chemistry "U. Schiff", University of Florence, Via della Lastruccia 3, 50019, Sesto Fiorentino, Italy.
Abstract:
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.
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