Combinatorial synthesis of substituted 3-(2-indolyl)piperidines and 2-phenyl indoles as inhibitors of ZipA-FtsZ interaction

Bioorg Med Chem. 2004 Oct 1;12(19):5115-31. doi: 10.1016/j.bmc.2004.07.031.

Abstract

The ZipA-FtsZ protein-protein interaction is a potential target for antibacterial therapy. The design and parallel synthesis of a combinatorial library of small molecules, which target the FtsZ binding area on ZipA are described. Compounds were demonstrated to bind to the FtsZ binding domain of ZipA by HSQC NMR and to inhibit cell division in a cell elongation assay.

MeSH terms

  • Anti-Bacterial Agents / chemical synthesis*
  • Anti-Bacterial Agents / pharmacology
  • Carrier Proteins / chemistry*
  • Cell Cycle Proteins / chemistry*
  • Cell Division / drug effects
  • Combinatorial Chemistry Techniques
  • Escherichia coli / cytology
  • Escherichia coli / drug effects
  • Escherichia coli Proteins / chemistry*
  • Indoles / chemical synthesis*
  • Indoles / pharmacology
  • Inhibitory Concentration 50
  • Piperidines / chemical synthesis*
  • Piperidines / pharmacology
  • Protein Binding / drug effects
  • Structure-Activity Relationship

Substances

  • Anti-Bacterial Agents
  • Carrier Proteins
  • Cell Cycle Proteins
  • Escherichia coli Proteins
  • FtsZ84 protein, E coli
  • Indoles
  • Piperidines
  • ZipA protein, E coli