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2-Aminotetralones: novel inhibitors of MurA and MurZ

Authors :
Katy L. Blake
James A. Garnett
Jennifer A. Leeds
Simon E. V. Phillips
Peter J. F. Henderson
Deborah Palestrant
Simon G. Patching
Ian Chopra
Colin J. Dunsmore
Colin W. G. Fishwick
Keith W. Miller
Joseph E. de los Angeles
William J. Stubbings
The Astbury Centre for Structural Molecular Biology
University of Leeds
School of Biomedical Sciences, University of Leeds
Source :
Bioorganic and Medicinal Chemistry Letters, Bioorganic and Medicinal Chemistry Letters, Elsevier, 2008, 18 (5), pp.1730-1734. ⟨10.1016/j.bmcl.2008.01.089⟩
Publication Year :
2007

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 microg/ml. Based on structure-activity relationships we propose that the alpha-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.

Details

ISSN :
14643405 and 0960894X
Volume :
18
Issue :
5
Database :
OpenAIRE
Journal :
Bioorganicmedicinal chemistry letters
Accession number :
edsair.doi.dedup.....d49ba11a238d8f507d44bd876fc535c8
Full Text :
https://doi.org/10.1016/j.bmcl.2008.01.089⟩