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 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.
Dunsmore
Colin J
CJ
School of Chemistry and Antimicrobial Research Centre, University of Leeds, Leeds LS2 9JT, UK.
Miller
Keith
K
Blake
Katy L
KL
Patching
Simon G
SG
Henderson
Peter J F
PJ
Garnett
James A
JA
Stubbings
William J
WJ
Phillips
Simon E V
SE
Palestrant
Deborah J
DJ
Angeles
Joseph De Los
Jde L
Leeds
Jennifer A
JA
Chopra
Ian
I
Fishwick
Colin W G
CW
D000900:Anti-Bacterial Agents / Q000737:chemistry* / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000037:antagonists & inhibitors*; D001665:Binding Sites; D004926:Escherichia coli / Q000187:drug effects; D008826:Microbial Sensitivity Tests; D008958:Models, Molecular; D015394:Molecular Structure; D013211:Staphylococcus aureus / Q000187:drug effects; D013329:Structure-Activity Relationship; D044024:Tetralones / Q000737:chemistry* / Q000494:pharmacology*
D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D044024:Tetralones