Journal
CHEMBIOCHEM
Volume 22, Issue 6, Pages 1093-1098Publisher
WILEY-V C H VERLAG GMBH
DOI: 10.1002/cbic.202000707
Keywords
antibiotic resistance; antibiotics; inhibitors; NHC-metal complexes; thioredoxin reductase
Funding
- UCD School of Chemistry
- Royal Embassy of Saudi Arabia
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A novel antibiotic candidate compound, SBC3, combining silver salt with inhibition of E. coli growth, has been discovered with high affinity and efficacy against Gram-negative bacteria.
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.
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