Synthesis and biological evaluation of new glutamic acid-based inhibitors of MurD ligase.
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.
Tomasić
Tihomir
T
University of Ljubljana, Faculty of Pharmacy, Ljubljana, Slovenia.
Zidar
Nace
N
Rupnik
Veronika
V
Kovac
Andreja
A
Blanot
Didier
D
Gobec
Stanislav
S
Kikelj
Danijel
D
Masic
Lucija Peterlin
LP
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
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