Bioorg Med Chem Lett. 2009 Jan 1;19(1):153-7. Epub 2008 Nov 5.

Synthesis and biological evaluation of new glutamic acid-based inhibitors of MurD ligase.

Tomasić T, Zidar N, Rupnik V, Kovac A, Blanot D, Gobec S, Kikelj D, Masic LP.

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University of Ljubljana, Faculty of Pharmacy, Ljubljana, Slovenia.

Abstract

Mur ligases catalyze the biosynthesis of the UDP-MurNAc-pentapeptide precursor of peptidoglycan, an essential polymer of bacterial cell-wall. They constitute attractive targets for the development of novel antibacterial agents. Here we report on the synthesis of a series of 2,4-diaminoquinazolines, quinazoline-2,4(1H,3H)-diones, 5-benzylidenerhodanines and 5-benzylidenethiazolidine-2,4-diones and their inhibitory activities against MurD from Escherichia coli. Compounds (R)-27 and (S)-27 showed inhibitory activity against MurD with IC(50) values of 174 and 206 microM, respectively, which makes them promising starting points for optimization.

PMID:: 19014883; [PubMed - indexed for MEDLINE]

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