Design, Synthesis and in vitro Biochemical Activity of Novel Amino Acid Sulfonohydrazide Inhibitors of MurC

摘要

Mur ligases are essential enzymes involved in the cytoplasmic steps of peptidoglycan synthesis which remain attractive, yet unexploited targets. In order to develop new antibacterial agents, we have designed a series of new MurC and Mur-D inhibitors bearing amino acid sulfonohydrazide moiety. The L-Leu series of this class displayed the highest enzyme inhibition with IC_(50) in the concentration range between 100 and 500 uM, with L-Thr, L-Pro and L-Ala derivatives being inactive. The most promising compound of the series also expressed weak antibacterial activity against S. aureus with MIC = 128 μg/mL.