Recent advances in the discovery and development of antibacterial agents targeting the cell-division protein FtsZ

Bioorg Med Chem. 2016 Dec 15;24(24):6354-6369. doi: 10.1016/j.bmc.2016.05.003. Epub 2016 May 5.

Abstract

With the emergence of multidrug-resistant bacterial strains, there is a dire need for new drug targets for antibacterial drug discovery and development. Filamentous temperature sensitive protein Z (FtsZ), is a GTP-dependent prokaryotic cell division protein, sharing less than 10% sequence identity with the eukaryotic cell division protein, tubulin. FtsZ forms a dynamic Z-ring in the middle of the cell, leading to septation and subsequent cell division. Inhibition of the Z-ring blocks cell division, thus making FtsZ a highly attractive target. Various groups have been working on natural products and synthetic small molecules as inhibitors of FtsZ. This review summarizes the recent advances in the development of FtsZ inhibitors, focusing on those in the last 5years, but also includes significant findings in previous years.

Keywords: Antibacterial agent; Cell division; FtsZ; Inhibitor; Multidrug resistance; Septation; Z-ring protofilament.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't
  • Research Support, N.I.H., Extramural

MeSH terms

  • Anti-Bacterial Agents / chemical synthesis
  • Anti-Bacterial Agents / chemistry
  • Anti-Bacterial Agents / pharmacology*
  • Bacteria / chemistry
  • Bacteria / cytology
  • Bacteria / drug effects*
  • Bacterial Proteins / antagonists & inhibitors*
  • Cytoskeletal Proteins / antagonists & inhibitors*
  • Drug Discovery*
  • Humans
  • Microbial Sensitivity Tests
  • Structure-Activity Relationship

Substances

  • Anti-Bacterial Agents
  • Bacterial Proteins
  • Cytoskeletal Proteins
  • FtsZ protein, Bacteria