Triketones active against antibiotic-resistant bacteria: synthesis, structure-activity relationships, and mode of action

John W van Klink; Lesley Larsen; Nigel B Perry; Rex T Weavers; Gregory M Cook; Phil J Bremer; Andrew D MacKenzie; Teruo Kirikae

doi:10.1016/j.bmc.2005.07.045

Triketones active against antibiotic-resistant bacteria: synthesis, structure-activity relationships, and mode of action

Bioorg Med Chem. 2005 Dec 15;13(24):6651-62. doi: 10.1016/j.bmc.2005.07.045. Epub 2005 Sep 1.

Authors

John W van Klink¹, Lesley Larsen, Nigel B Perry, Rex T Weavers, Gregory M Cook, Phil J Bremer, Andrew D MacKenzie, Teruo Kirikae

Affiliation

¹ New Zealand Institute for Crop & Food Research Ltd, University of Otago, PO Box 56 Dunedin, New Zealand. vanklinkj@crop.cri.nz

PMID: 16140015
DOI: 10.1016/j.bmc.2005.07.045

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Anti-Bacterial Agents / chemical synthesis*
Anti-Bacterial Agents / chemistry
Anti-Bacterial Agents / pharmacology*
Drug Resistance, Bacterial*
Enterococcus faecalis / drug effects
Ketones / chemical synthesis*
Ketones / chemistry
Ketones / pharmacology*
Magnetic Resonance Spectroscopy
Models, Chemical
Molecular Structure
Mycobacterium tuberculosis / drug effects
Staphylococcus aureus / drug effects
Structure-Activity Relationship

Substances

Anti-Bacterial Agents
Ketones