Dual inhibitor of MurD and MurE ligases from Escherichia coli and Staphylococcus aureus
Tomašič, Tihomir ...
MurD and MurE ligases, consecutive enzymes participating in the intracellular steps of bacterial peptidoglycan biosynthesis, are important targets for antibacterial drug discovery. We have designed, ...synthesized and evaluated the first D-glutamic acid-containing dual inhibitor of MurD and MurE ligases from Escherichia coli and Staphylococcus aureus (IC50s between 6.4 and 180 [micro]M possessing antibacterial activity against Gram-positive S. aureus and its methicillin-resistant strain (MRSA) with minimal inhibitory concentration (MIC) values of 8 [micro]g/mL. The inhibitor was also found to be non-cytotoxic for human HepG2 cells at concentrations below 200 [micro]M.
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