Abstract
Small-molecule inhibitors of the mycobacterial transcriptional repressor EthR have previously been shown to act as boosters of the second-line antituberculosis drug ethionamide. Fragment-based drug discovery approaches have been used in the past to make highly potent EthR inhibitors with ethionamide boosting activity both in vitro and ex vivo. Herein, we report the development of fragment-sized EthR ligands with nanomolar minimum effective concentration values for boosting the ethionamide activity in Mycobacterium tuberculosis whole-cell assays.
Publication types
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Research Support, N.I.H., Intramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Antitubercular Agents
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Bacterial Proteins
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Drug Discovery
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Drug Synergism
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Enzyme Inhibitors / pharmacology
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Enzyme Inhibitors / therapeutic use
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Ethionamide / pharmacology*
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Ethionamide / therapeutic use
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Ligands
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Microbial Sensitivity Tests
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Mycobacterium tuberculosis / drug effects
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Mycobacterium tuberculosis / enzymology*
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Repressor Proteins / antagonists & inhibitors*
Substances
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Antitubercular Agents
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Bacterial Proteins
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Enzyme Inhibitors
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EthR protein, Mycobacterium tuberculosis
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Ligands
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Repressor Proteins
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Ethionamide