Structure-based discovery of LpxC inhibitors

Bioorg Med Chem Lett. 2017 Apr 15;27(8):1670-1680. doi: 10.1016/j.bmcl.2017.03.006. Epub 2017 Mar 6.

Abstract

The emergence and spread of multidrug-resistant (MDR) Gram negative bacteria presents a serious threat for public health. Novel antimicrobials that could overcome the resistance problems are urgently needed. UDP-3-O-(R-3-hydroxymyristol)-N-acetylglucosamine deacetylase (LpxC) is a cytosolic zinc-based deacetylase that catalyzes the first committed step in the biosynthesis of lipid A, which is essential for the survival of Gram-negative bacteria. Our efforts toward the discovery of novel LpxC inhibitors are presented herein.

Keywords: Acinetobacter baumannii; Antibacterial; Escherichia coli; Klebsiella pneumonia; LpxC; Pseudomonas aeruginosa.

MeSH terms

  • Amidohydrolases / antagonists & inhibitors*
  • Amidohydrolases / metabolism
  • Anti-Bacterial Agents / chemistry*
  • Anti-Bacterial Agents / pharmacology*
  • Drug Discovery
  • Enzyme Inhibitors / chemistry*
  • Enzyme Inhibitors / pharmacology*
  • Gram-Negative Bacteria / drug effects*
  • Gram-Negative Bacteria / enzymology*
  • Gram-Negative Bacterial Infections / drug therapy
  • Humans
  • Molecular Docking Simulation

Substances

  • Anti-Bacterial Agents
  • Enzyme Inhibitors
  • Amidohydrolases
  • N-acetylglucosamine deacetylase