Abstract
Bacterial resistance presents a difficult issue for fluoroquinolone treatment of bacterial infections. In previous work, we reported that 8-methoxy-quinazoline-2,4-diones are active against quinolone-resistant mutants of Escherichia coli. Here, we demonstrate the activity of a representative 8-methoxy-quinazoline-2,4-dione against quinolone-resistant gyrases. Furthermore, 8-methoxy-quinazoline-2,4-dione and other diones are shown to inhibit Staphylococcus aureus gyrase and topoisomerase IV with similar degrees of efficacy, suggesting that the diones might act as dual-targeting agents against S. aureus.
Publication types
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Research Support, N.I.H., Extramural
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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 / pharmacology*
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DNA Gyrase / metabolism
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DNA Topoisomerase IV / metabolism
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Enzyme Activation / drug effects
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Escherichia coli / drug effects
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Escherichia coli / enzymology
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Escherichia coli / genetics
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Fluoroquinolones / chemistry
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Fluoroquinolones / pharmacology*
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Microbial Sensitivity Tests
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Molecular Structure
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Staphylococcus aureus / drug effects
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Staphylococcus aureus / enzymology
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Staphylococcus aureus / genetics
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Viral Proteins / metabolism
Substances
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Anti-Bacterial Agents
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Fluoroquinolones
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Viral Proteins
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DNA Topoisomerase IV
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DNA Gyrase