Journal
CHEMMEDCHEM
Volume 13, Issue 22, Pages 2448-2454Publisher
WILEY-V C H VERLAG GMBH
DOI: 10.1002/cmdc.201800498
Keywords
antimicrobial drugs; auranofin; drug repositioning; drug resistance; gold compounds
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Funding
- Beneficentia Stiftung (Vaduz)
- Fondazione Cassa Risparmio Firenze (CRF)
- AIRC [IG-16049]
- COST Action [CM1105]
- AIRC-FIRC (Fondazione Italiana per la Ricerca sul Cancro, three-year Fellowship for Italy) [18044]
- ITT (Istituto Toscano Tumori)
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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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