2-Aminotetralones: Novel inhibitors of MurA and MurZ

Colin J. Dunsmore; Keith Miller; Katy L. Blake; Simon G. Patching; Peter J.F. Henderson; James A. Garnett; William J. Stubbings; Simon E.V. Phillips; Deborah J. Palestrant; Joseph De Los Angeles; Jennifer A. Leeds; Ian Chopra; Colin W.G. Fishwick

doi:10.1016/j.bmcl.2008.01.089

2-Aminotetralones: Novel inhibitors of MurA and MurZ

Colin J. Dunsmore, Keith Miller, Katy L. Blake, Simon G. Patching, Peter J.F. Henderson, James A. Garnett, William J. Stubbings, Simon E.V. Phillips, Deborah J. Palestrant, Joseph De Los Angeles, Jennifer A. Leeds, Ian Chopra, Colin W.G. Fishwick^*

^*Corresponding author for this work

Centre for Host Microbiome Interactions

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

33 Citations (Scopus)

Abstract

Several 2-aminotetralones were identified as novel inhibitors of the bacterial enzymes MurA and MurZ. A number of these inhibitors demonstrated antibacterial activity against Staphylococcus aureus and Escherichia coli with MICs in the range 8-128 μg/ml. Based on structure-activity relationships we propose that the α-aminoketone functionality is responsible for the inhibitory activity and evidence is provided to support a covalent mode of action involving the C115 thiol group of MurA/MurZ.

Original language	English
Pages (from-to)	1730-1734
Number of pages	5
Journal	BIOORGANIC AND MEDICINAL CHEMISTRY LETTERS
Volume	18
Issue number	5
DOIs	https://doi.org/10.1016/j.bmcl.2008.01.089
Publication status	Published - 1 Mar 2008

Keywords

2-Aminotetralone
Antibacterial activity
MurA inhibitor
MurZ inhibitor

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.bmcl.2008.01.089

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Dunsmore, C. J., Miller, K., Blake, K. L., Patching, S. G., Henderson, P. J. F., Garnett, J. A., Stubbings, W. J., Phillips, S. E. V., Palestrant, D. J., Angeles, J. D. L., Leeds, J. A., Chopra, I., & Fishwick, C. W. G. (2008). 2-Aminotetralones: Novel inhibitors of MurA and MurZ. BIOORGANIC AND MEDICINAL CHEMISTRY LETTERS, 18(5), 1730-1734. https://doi.org/10.1016/j.bmcl.2008.01.089

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title = "2-Aminotetralones: Novel inhibitors of MurA and MurZ",

abstract = "Several 2-aminotetralones were identified as novel inhibitors of the bacterial enzymes MurA and MurZ. A number of these inhibitors demonstrated antibacterial activity against Staphylococcus aureus and Escherichia coli with MICs in the range 8-128 μg/ml. Based on structure-activity relationships we propose that the α-aminoketone functionality is responsible for the inhibitory activity and evidence is provided to support a covalent mode of action involving the C115 thiol group of MurA/MurZ.",

keywords = "2-Aminotetralone, Antibacterial activity, MurA inhibitor, MurZ inhibitor",

author = "Dunsmore, {Colin J.} and Keith Miller and Blake, {Katy L.} and Patching, {Simon G.} and Henderson, {Peter J.F.} and Garnett, {James A.} and Stubbings, {William J.} and Phillips, {Simon E.V.} and Palestrant, {Deborah J.} and Angeles, {Joseph De Los} and Leeds, {Jennifer A.} and Ian Chopra and Fishwick, {Colin W.G.}",

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T2 - Novel inhibitors of MurA and MurZ

AU - Dunsmore, Colin J.

AU - Miller, Keith

AU - Blake, Katy L.

AU - Patching, Simon G.

AU - Henderson, Peter J.F.

AU - Garnett, James A.

AU - Stubbings, William J.

AU - Phillips, Simon E.V.

AU - Palestrant, Deborah J.

AU - Angeles, Joseph De Los

AU - Leeds, Jennifer A.

AU - Chopra, Ian

AU - Fishwick, Colin W.G.

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AB - Several 2-aminotetralones were identified as novel inhibitors of the bacterial enzymes MurA and MurZ. A number of these inhibitors demonstrated antibacterial activity against Staphylococcus aureus and Escherichia coli with MICs in the range 8-128 μg/ml. Based on structure-activity relationships we propose that the α-aminoketone functionality is responsible for the inhibitory activity and evidence is provided to support a covalent mode of action involving the C115 thiol group of MurA/MurZ.

KW - 2-Aminotetralone

KW - Antibacterial activity

KW - MurA inhibitor

KW - MurZ inhibitor

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JF - BIOORGANIC AND MEDICINAL CHEMISTRY LETTERS

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ER -

2-Aminotetralones: Novel inhibitors of MurA and MurZ

Abstract

Keywords

UN SDGs

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