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The Antibacterial Drug Candidate SBC3 is a Potent Inhibitor of Bacterial Thioredoxin Reductase
Author(s) -
O'Loughlin Jennie,
Napolitano Silvia,
Alkhathami Fahad,
O'Beirne Cillian,
Marhöfer Daniel,
O'Shaughnessy Megan,
Howe Orla,
Tacke Matthias,
Rubini Marina
Publication year - 2021
Publication title -
chembiochem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.05
H-Index - 126
eISSN - 1439-7633
pISSN - 1439-4227
DOI - 10.1002/cbic.202000707
Subject(s) - thioredoxin reductase , antibiotics , antimicrobial , escherichia coli , thioredoxin , chemistry , gentamicin , reductase , antibiotic resistance , drug , microbiology and biotechnology , drug resistance , enzyme , biochemistry , pharmacology , biology , gene
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; K i =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.