The Antibacterial Drug Candidate SBC3 is a Potent Inhibitor of Bacterial Thioredoxin Reductase

Antibiotic resistance is a growing problem for public health and associated with increasing economic costs and mortality rates. Silver and silver‐related compounds have been used for centuries due to their antimicrobial properties. In this work, we show that 1,3‐dibenzyl‐4,5‐diphenyl‐imidazol‐2‐ylid...

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Published inChembiochem : a European journal of chemical biology Vol. 22; no. 6; pp. 1093 - 1098
Main Authors O'Loughlin, Jennie, Napolitano, Silvia, Alkhathami, Fahad, O'Beirne, Cillian, Marhöfer, Daniel, O'Shaughnessy, Megan, Howe, Orla, Tacke, Matthias, Rubini, Marina
Format Journal Article
LanguageEnglish
Published Germany Wiley Subscription Services, Inc 16.03.2021
Subjects
Acetic acid
Antibiotic resistance
Antibiotics
Antiinfectives and antibacterials
Bacteria
E coli
Economic impact
Gentamicin
Inhibitors
Minimum inhibitory concentration
NHC-metal complexes
Public health
Reductases
Silver
Thioredoxin
thioredoxin reductase
NHC-metal complexes
inhibitors
antibiotic resistance
antibiotics
thioredoxin reductase
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Summary:Antibiotic resistance is a growing problem for public health and associated with increasing economic costs and mortality rates. Silver and silver‐related compounds have been used for centuries due to their antimicrobial properties. In this work, we show that 1,3‐dibenzyl‐4,5‐diphenyl‐imidazol‐2‐ylidene silver(I) acetate/NHC*‐Ag‐OAc (SBC3) is a reversible, high affinity inhibitor of E. coli thioredoxin reductase (TrxR; Ki=10.8±1.2 nM). Minimal inhibition concentration (MIC) tests with different E. coli and P. aeruginosa strains demonstrated that SBC3 can efficiently inhibit bacterial cell growth, especially in combination with established antibiotics like gentamicin. Our results show that SBC3 is a promising antibiotic drug candidate targeting bacterial TrxR. Silver lining: Antibiotic resistance jeopardizes the effective treatment of infectious diseases and represents an increasing threat to public health. We discovered that the N‐heterocyclic carbene 1,3‐dibenzyl‐4,5‐diphenylimidazol‐2‐ylidene silver(I) acetate (SBC3) is a potent inhibitor of bacterial thioredoxin reductase that proved to be highly effective against resistant Gram‐negative nosocomial isolates.
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ISSN:1439-4227
1439-7633
DOI:10.1002/cbic.202000707