title: Triketones active against antibiotic-resistant bacteria: synthesis, structure-activity relationships, and mode of action.
abstract: A series of acylated phloroglucinols and triketones was synthesized and tested for activity against methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant Enterococcus faecalis (VRE) and multi-drug-resistant Mycobacterium tuberculosis (MDR-TB). A tetra-methylated triketone with a C12 side chain was the most active compound (MIC of around 1.0 microg/ml against MRSA) and was shown to stimulate oxygen consumption by resting cell suspensions, suggesting that the primary target was the cytoplasmic membrane.
authors.affiliation: New Zealand Institute for Crop & Food Research Ltd, University of Otago, PO Box 56 Dunedin, New Zealand. vanklinkj@crop.cri.nz
authors.forename: John W
authors.initials: JW
authors.lastname: van Klink
authors.forename: Lesley
authors.initials: L
authors.lastname: Larsen
authors.forename: Nigel B
authors.initials: NB
authors.lastname: Perry
authors.forename: Rex T
authors.initials: RT
authors.lastname: Weavers
authors.forename: Gregory M
authors.initials: GM
authors.lastname: Cook
authors.forename: Phil J
authors.initials: PJ
authors.lastname: Bremer
authors.forename: Andrew D
authors.initials: AD
authors.lastname: MacKenzie
authors.forename: Teruo
authors.initials: T
authors.lastname: Kirikae
mesh_terms: D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D024881:Drug Resistance, Bacterial; D013293:Enterococcus faecalis / Q000187:drug effects; D007659:Ketones / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D009682:Magnetic Resonance Spectroscopy; D008956:Models, Chemical; D015394:Molecular Structure; D009169:Mycobacterium tuberculosis / Q000187:drug effects; D013211:Staphylococcus aureus / Q000187:drug effects; D013329:Structure-Activity Relationship
chemical_list: D000900:Anti-Bacterial Agents; D007659:Ketones