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Carboxylic acid isosteres improve the activity of ring-fused 2-pyridones that inhibit pilus biogenesis in E. coli.

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.

SUBMITTER: Berg V

PROVIDER: S-EPMC3665338 | biostudies-literature | 2008 Jun

REPOSITORIES: biostudies-literature

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Carboxylic acid isosteres improve the activity of ring-fused 2-pyridones that inhibit pilus biogenesis in E. coli.

Berg Veronica V Das Pralay P Chorell Erik E Hedenström Mattias M Pinkner Jerome S JS Hultgren Scott J SJ Almqvist Fredrik F

Bioorganic & medicinal chemistry letters 20080507 12

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 significan ...[more]

PMID: 18499455

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