Title:MurF Ligase Inhibitors: An Overview of Antibacterial Activity
Volume: 20
Issue: 11
Author(s): Anjali Singh and Mohammed Afzal Azam*
Affiliation:
- Department of Pharmaceutical Chemistry, JSS College of Pharmacy, JSS Academy of Higher Education and Research,
Ooty, Nilgiris, Tamil Nadu, India
Keywords:
MurF enzyme, antibacterial activity, MIC, IC50, aminoalkylphosphinates, phosphorylated hydroxylamines, azastilbene derivatives.
Abstract: ATP dependent MurC-F ligases are essential for the biosynthesis of peptidoglycan, an essential
bacterial cell wall component that is required for bacterial cell survival. Last, in the series, MurF catalyzes
the ATP-dependent addition of D-Ala-D-Ala dipeptide to UDP-N-acetylmuramyl-tripeptide to form the
UDP-N-acetylmuramy-pentapeptide monomeric precursor of peptidoglycan. Owing to its critical essentiality
in peptidoglycan biosynthesis and absence in eukaryotic counterparts, MurF is considered a promising
target for the design and development of potent antibacterial agents. Several MurF inhibitors have
been designed and evaluated for their MurF inhibitory and antibacterial activity. These include aminoalkylphosphinates,
sulfonamides, diarylquinolones, hydroxylamines, phosphorylated hydroxylamines, thiazolylaminopyrimidines,
2,4,6-trisubstituted 1,3,5-triazines, etc. However, most of the inhibitors developed
till date lack potent antibacterial activity against both Gram-positive and Gram-negative bacteria. In
the present review, an updated status of MurF ligase inhibitors is presented that may provide a useful
source for the design of novel MurF inhibitors with potent and broad-spectrum antibacterial activity.