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.
Keywords:
NHC-metal complexes; antibiotic resistance; antibiotics; inhibitors; thioredoxin reductase.
© 2020 Wiley-VCH GmbH.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Anti-Bacterial Agents / chemistry*
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Anti-Bacterial Agents / metabolism
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Anti-Bacterial Agents / pharmacology
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Coordination Complexes / chemistry
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Coordination Complexes / metabolism
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Coordination Complexes / pharmacology
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Escherichia coli / drug effects
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Escherichia coli / enzymology
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Escherichia coli Proteins / antagonists & inhibitors*
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Escherichia coli Proteins / metabolism
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Gentamicins / pharmacology
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Imidazolines / chemistry
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Imidazolines / metabolism
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Imidazolines / pharmacology
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Kinetics
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Microbial Sensitivity Tests
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Organometallic Compounds / chemistry
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Organometallic Compounds / metabolism
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Organometallic Compounds / pharmacology
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Pseudomonas aeruginosa / drug effects
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Thioredoxin-Disulfide Reductase / antagonists & inhibitors*
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Thioredoxin-Disulfide Reductase / metabolism
Substances
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1,3-dibenzyl-4,5-diphenyl-imidazol-2-ylidene silver(I) acetate
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Anti-Bacterial Agents
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Coordination Complexes
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Escherichia coli Proteins
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Gentamicins
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Imidazolines
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Organometallic Compounds
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Thioredoxin-Disulfide Reductase