Bacterial transferase MraY inhibitors: Synthesis and biological evaluation

• Published in: Bioorganic & medicinal chemistry 2010-06, Vol.18 (12), p.4560-4569
• Main Authors: Lecerclé, Delphine, Clouet, Anthony, Al-Dabbagh, Bayan, Crouvoisier, Muriel, Bouhss, Ahmed, Gravier-Pelletier, Christine, Le Merrer, Yves
• Format: Article
• Language: English
• Subjects: Anti-Bacterial Agents - chemical synthesis; Anti-Bacterial Agents - chemistry; Anti-Bacterial Agents - pharmacology; Antibacterial agents; Antibiotics. Antiinfectious agents. Antiparasitic agents; Bacillus subtilis - enzymology; Bacterial Proteins - antagonists & inhibitors; Bacterial Proteins - metabolism; Bacterial transferase MraY; Biological and medical sciences; Bis-epoxide; Cycloaddition; Enzyme Inhibitors - chemical synthesis; Enzyme Inhibitors - chemistry; Enzyme Inhibitors - pharmacology; Glycosylation; Inhibition; Medical sciences; Pharmacology. Drug treatments; Transferases - antagonists & inhibitors; Transferases - metabolism; Triazole; Triazoles - chemical synthesis; Triazoles - chemistry; Triazoles - pharmacology
• ISSN: 0968-0896; 1464-3391
• DOI: 10.1016/j.bmc.2010.04.023

New inhibitors of the bacterial transferase MraY are described. Their structure is based on an aminoribosyl- O-uridine like scaffold, readily obtained in two key steps. The amino group can be coupled with proline or guanylated. Alternatively, these amino, prolinyl or guanidinyl groups can be introduced through a triazole linker. Biological evaluation of these compounds on MraY from Bacillus subtilis revealed interesting inhibitory activity for both amino compounds.