2y68

Publication Abstract from PubMed

MurD ligase is one of the key enzymes participating in the intracellular steps of peptidoglycan biosynthesis and constitutes a viable target in the search for novel antibacterial drugs to combat bacterial drug-resistance. We have designed, synthesized, and evaluated a new series of d-glutamic acid-based Escherichia coli MurD inhibitors incorporating the 5-benzylidenethiazolidin-4-one scaffold. The crystal structure of 16 in the MurD active site has provided a good starting point for the design of structurally optimized inhibitors 73-75 endowed with improved MurD inhibitory potency (IC(50) between 3 and 7 muM). Inhibitors 74 and 75 showed weak activity against Gram-positive Staphylococcus aureus and Enterococcus faecalis. Compounds 73-75, with IC(50) values in the low micromolar range, represent the most potent d-Glu-based MurD inhibitors reported to date.

Structure-Based Design of a New Series of d-Glutamic Acid Based Inhibitors of Bacterial UDP-N-acetylmuramoyl-l-alanine:d-glutamate Ligase (MurD).,Tomasic T, Zidar N, Sink R, Kovac A, Blanot D, Contreras-Martel C, Dessen A, Muller-Premru M, Zega A, Gobec S, Kikelj D, Peterlin Masic L J Med Chem. 2011 Jun 3. PMID:21591605^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.