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

ChemMedChem. 2018 Nov 20;13(22):2448-2454. doi: 10.1002/cmdc.201800498. Epub 2018 Nov 5.

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.

Keywords: antimicrobial drugs; auranofin; drug repositioning; drug resistance; gold compounds.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Bacterial Agents / chemical synthesis
  • Anti-Bacterial Agents / chemistry
  • Anti-Bacterial Agents / pharmacology*
  • Antifungal Agents / chemical synthesis
  • Antifungal Agents / chemistry
  • Antifungal Agents / pharmacology*
  • Auranofin / chemical synthesis
  • Auranofin / chemistry
  • Auranofin / pharmacology*
  • Candida albicans / drug effects
  • Coordination Complexes / chemical synthesis
  • Coordination Complexes / chemistry
  • Coordination Complexes / pharmacology*
  • Drug Resistance, Multiple, Bacterial / drug effects
  • Gold / chemistry
  • Gram-Negative Bacteria / drug effects
  • Gram-Positive Bacteria / drug effects
  • Microbial Sensitivity Tests
  • Molecular Structure
  • Silver / chemistry
  • Structure-Activity Relationship

Substances

  • Anti-Bacterial Agents
  • Antifungal Agents
  • Coordination Complexes
  • Auranofin
  • Silver
  • Gold