Triketones active against antibiotic-resistant bacteria: synthesis, structure-activity relationships, and mode of action.
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.
van Klink
John W
JW
New Zealand Institute for Crop & Food Research Ltd, University of Otago, PO Box 56 Dunedin, New Zealand. vanklinkj@crop.cri.nz
Larsen
Lesley
L
Perry
Nigel B
NB
Weavers
Rex T
RT
Cook
Gregory M
GM
Bremer
Phil J
PJ
MacKenzie
Andrew D
AD
Kirikae
Teruo
T
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
D000900:Anti-Bacterial Agents; D007659:Ketones