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Auranofin and its Analogues Show Potent Antimicrobial Activity against Multidrug‐Resistant Pathogens: Structure–Activity Relationships
Author(s) -
Marzo Tiziano,
Cirri Damiano,
Pollini Simona,
Prato Marco,
Fallani Stefania,
Cassetta Maria Iris,
Novelli Andrea,
Rossolini Gian Maria,
Messori Luigi
Publication year - 2018
Publication title -
chemmedchem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.817
H-Index - 100
eISSN - 1860-7187
pISSN - 1860-7179
DOI - 10.1002/cmdc.201800498
Subject(s) - auranofin , antimicrobial , multiple drug resistance , antibacterial activity , mode of action , antibiotics , microbiology and biotechnology , chemistry , structure–activity relationship , gold compounds , stereochemistry , combinatorial chemistry , bacteria , biology , in vitro , biochemistry , immunology , rheumatoid arthritis , genetics
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(PEt 3 )X] (with M=Au or Ag, and X=Cl, Br or I), alongside with three complexes bearing a positive or negative charge—[Au(PEt 3 ) 2 ]Cl, K[Au(CN) 2 ] and [Ag(PEt 3 ) 2 ]NO 3 —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.