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 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.
authors.affiliation: School of Chemistry and Antimicrobial Research Centre, University of Leeds, Leeds LS2 9JT, UK.
authors.forename: Colin J
authors.initials: CJ
authors.lastname: Dunsmore
authors.forename: Keith
authors.initials: K
authors.lastname: Miller
authors.forename: Katy L
authors.initials: KL
authors.lastname: Blake
authors.forename: Simon G
authors.initials: SG
authors.lastname: Patching
authors.forename: Peter J F
authors.initials: PJ
authors.lastname: Henderson
authors.forename: James A
authors.initials: JA
authors.lastname: Garnett
authors.forename: William J
authors.initials: WJ
authors.lastname: Stubbings
authors.forename: Simon E V
authors.initials: SE
authors.lastname: Phillips
authors.forename: Deborah J
authors.initials: DJ
authors.lastname: Palestrant
authors.forename: Joseph De Los
authors.initials: Jde L
authors.lastname: Angeles
authors.forename: Jennifer A
authors.initials: JA
authors.lastname: Leeds
authors.forename: Ian
authors.initials: I
authors.lastname: Chopra
authors.forename: Colin W G
authors.initials: CW
authors.lastname: Fishwick
mesh_terms: 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*
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D044024:Tetralones