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

Veronica Åberg; Pralay Das; Erik Chorell; Mattias Hedenström; Jerome S. Pinkner; Scott J. Hultgren; Fredrik Almqvist

doi:10.1016/j.bmcl.2008.05.020

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

Veronica Åberg, Pralay Das, Erik Chorell, Mattias Hedenström, Jerome S. Pinkner, Scott J. Hultgren, Fredrik Almqvist

Research output: Contribution to journal › Article › peer-review

29 Scopus citations

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.

Original language	English
Pages (from-to)	3536-3540
Number of pages	5
Journal	Bioorganic and Medicinal Chemistry Letters
Volume	18
Issue number	12
DOIs	https://doi.org/10.1016/j.bmcl.2008.05.020
State	Published - Jun 15 2008

Keywords

2-Pyridone
Antimicrobial
Bioisostere
Escherichia coli
Pili
Pilicide

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10.1016/j.bmcl.2008.05.020

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title = "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.",

keywords = "2-Pyridone, Antimicrobial, Bioisostere, Escherichia coli, Pili, Pilicide",

author = "Veronica {\AA}berg and Pralay Das and Erik Chorell and Mattias Hedenstr{\"o}m and Pinkner, {Jerome S.} and Hultgren, {Scott J.} and Fredrik Almqvist",

note = "Funding Information: We thank the Swedish Natural Science Research Council and the Knut and Alice Wallenberg foundation for financial support. ",

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T1 - Carboxylic acid isosteres improve the activity of ring-fused 2-pyridones that inhibit pilus biogenesis in E. coli

AU - Åberg, Veronica

AU - Das, Pralay

AU - Chorell, Erik

AU - Hedenström, Mattias

AU - Pinkner, Jerome S.

AU - Hultgren, Scott J.

AU - Almqvist, Fredrik

N1 - Funding Information: We thank the Swedish Natural Science Research Council and the Knut and Alice Wallenberg foundation for financial support.

PY - 2008/6/15

Y1 - 2008/6/15

N2 - 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.

AB - 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.

KW - 2-Pyridone

KW - Antimicrobial

KW - Bioisostere

KW - Escherichia coli

KW - Pili

KW - Pilicide

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U2 - 10.1016/j.bmcl.2008.05.020

DO - 10.1016/j.bmcl.2008.05.020

M3 - Article

C2 - 18499455

AN - SCOPUS:44649199817

SN - 0960-894X

VL - 18

SP - 3536

EP - 3540

JO - Bioorganic and Medicinal Chemistry Letters

JF - Bioorganic and Medicinal Chemistry Letters

IS - 12

ER -

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

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Keywords

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