Bioorganic & Medicinal Chemistry Letters 2008-03-01

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

Index: Bioorg. Med. Chem. Lett. 18(5) , 1730-4, (2008)

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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.