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

Jennie O'Loughlin; Silvia Napolitano; Fahad Alkhathami; Cillian O'Beirne; Daniel Marhöfer; Megan O'Shaughnessy; Orla Howe; Matthias Tacke; Marina Rubini

doi:10.1002/cbic.202000707

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

Jennie O'Loughlin, Silvia Napolitano, Fahad Alkhathami, Cillian O'Beirne, Daniel Marhöfer, Megan O'Shaughnessy, Orla Howe, Matthias Tacke, Marina Rubini

Research output: Contribution to journal › Article › peer-review

14 Citations (Scopus)

Abstract

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.

Original language	English
Pages (from-to)	1093-1098
Number of pages	6
Journal	ChemBioChem
Volume	22
Issue number	6
DOIs	https://doi.org/10.1002/cbic.202000707
Publication status	Published - 16 Mar 2021

Keywords

antibiotic resistance
antibiotics
inhibitors
NHC-metal complexes
thioredoxin reductase

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10.1002/cbic.202000707

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abstract = "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.",

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AU - O'Beirne, Cillian

AU - Marhöfer, Daniel

AU - O'Shaughnessy, Megan

AU - Howe, Orla

AU - Tacke, Matthias

AU - Rubini, Marina

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AB - 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.

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

Abstract

Keywords

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