LpxC (UDP-3-O-(R-3-hydroxymyristoyl)-N-acetylglucosamine deacetylase) inhibitors: A long path explored for potent drug design

Int J Biol Macromol. 2023 Apr 15:234:122960. doi: 10.1016/j.ijbiomac.2022.12.179. Epub 2022 Dec 22.

Abstract

Microbial infections are becoming resistant to traditional antibiotics. As novel resistance mechanisms are developed and disseminated across the world, our ability to treat the most common infectious diseases is becoming increasingly compromised. As existing antibiotics are losing their effectiveness, especially treatment of bacterial infections, is difficult. In order to combat this issue, it is of utmost importance to identify novel pharmacological targets or antibiotics. LpxC, a zinc-dependent metalloamidase that catalyzes the committed step in the biosynthesis of lipid A (endotoxin) in bacteria, is a prime candidate for drug/therapeutic target. So far, the rate-limiting metallo-amidase LpxC has been the most-targeted macromolecule in the Raetz pathway. This is because it is important for the growth of these bacterial infections. This review showcases on the research done to develop efficient drugs in this area before and after the 2015.

Keywords: Drug discovery; Inhibition; Lipid A; LpxC; Raetz pathway.

Publication types

  • Review

MeSH terms

  • Amidohydrolases* / antagonists & inhibitors
  • Amidohydrolases* / metabolism
  • Animals
  • Anti-Bacterial Agents* / chemistry
  • Anti-Bacterial Agents* / pharmacology
  • Drug Design*
  • Drug Resistance, Microbial
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / pharmacology
  • Humans
  • Zinc / metabolism

Substances

  • Amidohydrolases
  • Anti-Bacterial Agents
  • Enzyme Inhibitors
  • UDP-3-O-acyl-N-acetylglucosamine deacetylase
  • Zinc