Reaching toward underexplored targets in antibacterial drug design

Drug Dev Res. 2019 Feb;80(1):6-10. doi: 10.1002/ddr.21465. Epub 2018 Oct 12.

Abstract

The increase of antimicrobial resistance necessitates the renewal and strong research involvement in antibacterial drug design. In the following work, we comment on the key approaches used in development of new antibacterials, focusing on intracellular therapeutic targets that have been so far mostly underexplored: the enzymes of the Mur pathway MurA to MurF. We identify common obstacles observed during research on MurA, MurB, and Mur ligases inhibitors and their development into potential antibacterial compounds, and discern several approaches and solutions to tackle the whole-cell activity of designed compounds. Furthermore, we consolidate recent literature reports and encourage the further research on Mur enzymes.

Keywords: Mur ligases; MurA; MurB; antibacterial; antimicrobial resistance; drug design.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Alkyl and Aryl Transferases / antagonists & inhibitors
  • Alkyl and Aryl Transferases / metabolism
  • Animals
  • Anti-Bacterial Agents / administration & dosage*
  • Anti-Bacterial Agents / metabolism
  • Drug Delivery Systems / methods*
  • Drug Delivery Systems / trends
  • Drug Design*
  • Enzyme Inhibitors / administration & dosage
  • Enzyme Inhibitors / metabolism
  • Humans

Substances

  • Anti-Bacterial Agents
  • Enzyme Inhibitors
  • Alkyl and Aryl Transferases
  • UDP-N-acetylglucosamine 1-carboxyvinyltransferase