Design and synthesis of indolo[2,3-a]quinolizin-7-one inhibitors of the ZipA-FtsZ interaction

Bioorg Med Chem Lett. 2004 Mar 22;14(6):1427-31. doi: 10.1016/j.bmcl.2004.01.028.

Abstract

The binding of FtsZ to ZipA is a potential target for antibacterial therapy. Based on a small molecule inhibitor of the ZipA-FtsZ interaction, a parallel synthesis of small molecules was initiated which targeted a key region of ZipA involved in FtsZ binding. The X-ray crystal structure of one of these molecules complexed with ZipA was solved. The structure revealed an unexpected binding mode, facilitated by desolvation of a loosely bound surface water.

MeSH terms

  • Amino Acid Sequence
  • Carrier Proteins / antagonists & inhibitors*
  • Carrier Proteins / metabolism*
  • Cell Cycle Proteins / antagonists & inhibitors*
  • Cell Cycle Proteins / metabolism*
  • Drug Design*
  • Escherichia coli Proteins / antagonists & inhibitors*
  • Escherichia coli Proteins / metabolism*
  • Indoles / chemical synthesis*
  • Indoles / chemistry
  • Indoles / metabolism
  • Molecular Sequence Data
  • Protein Binding / physiology
  • Quinazolines / chemical synthesis*
  • Quinazolines / chemistry
  • Quinazolines / metabolism

Substances

  • Carrier Proteins
  • Cell Cycle Proteins
  • Escherichia coli Proteins
  • FtsZ84 protein, E coli
  • Indoles
  • Quinazolines
  • ZipA protein, E coli
  • indolo(2,1-b)quinazoline