Abstract
Ring-fused 2-pyridones, termed pilicides, are small synthetic compounds that inhibit pilus assembly in uropathogenic Escherichia coli. Their biological activity is clearly dependent upon a carboxylic acid functionality. Here, we present the synthesis and biological evaluation of carboxylic acid isosteres, including, for example, tetrazoles, acyl sulfonamides, and hydroxamic acids of two lead 2-pyridones. Two independent biological evaluations show that acyl sulfonamides and tetrazoles significantly improve pilicide activity against uropathogenic E. coli.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Anti-Bacterial Agents / chemical synthesis
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Anti-Bacterial Agents / chemistry
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Anti-Bacterial Agents / pharmacology*
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Carboxylic Acids / chemical synthesis
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Carboxylic Acids / chemistry
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Carboxylic Acids / pharmacology*
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Dose-Response Relationship, Drug
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Escherichia coli / drug effects*
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Escherichia coli / metabolism
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Escherichia coli / pathogenicity
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Fimbriae, Bacterial / drug effects*
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Fimbriae, Bacterial / metabolism
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Microbial Sensitivity Tests
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Molecular Conformation
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Pyridones / chemistry*
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Stereoisomerism
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Structure-Activity Relationship
Substances
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Anti-Bacterial Agents
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Carboxylic Acids
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Pyridones
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2-hydroxypyridine