title: Synthesis and biological evaluation of new glutamic acid-based inhibitors of MurD ligase.
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.
authors.affiliation: University of Ljubljana, Faculty of Pharmacy, Ljubljana, Slovenia.
authors.forename: Tihomir
authors.initials: T
authors.lastname: Tomasić
authors.forename: Nace
authors.initials: N
authors.lastname: Zidar
authors.forename: Veronika
authors.initials: V
authors.lastname: Rupnik
authors.forename: Andreja
authors.initials: A
authors.lastname: Kovac
authors.forename: Didier
authors.initials: D
authors.lastname: Blanot
authors.forename: Stanislav
authors.initials: S
authors.lastname: Gobec
authors.forename: Danijel
authors.initials: D
authors.lastname: Kikelj
authors.forename: Lucija Peterlin
authors.initials: LP
authors.lastname: Masic
mesh_terms: D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D001597:Benzylidene Compounds / Q000138:chemical synthesis / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology; D004926:Escherichia coli / Q000201:enzymology; D018698:Glutamic Acid; D020128:Inhibitory Concentration 50; D010453:Peptide Synthases / Q000037:antagonists & inhibitors*; D011799:Quinazolines / Q000138:chemical synthesis / Q000494:pharmacology
chemical_list: D000900:Anti-Bacterial Agents; D001597:Benzylidene Compounds; D004791:Enzyme Inhibitors; D011799:Quinazolines; D018698:Glutamic Acid; D010453:Peptide Synthases; C053379:UDP-N-acetylmuramoylalanine-D-glutamate ligase