2-Aminotetralones: Novel inhibitors of MurA and MurZ

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.

A new series of inhibitors of Escherichia coli MurA and Staphylococcus aureus MurA and MurZ having useful antibacterial properties are reported.Figure optionsDownload as PowerPoint slide