Pyrrolamide DNA gyrase inhibitors: optimization of antibacterial activity and efficacy

Bioorg Med Chem Lett. 2011 Dec 15;21(24):7416-20. doi: 10.1016/j.bmcl.2011.10.010. Epub 2011 Oct 12.

Abstract

The pyrrolamides are a new class of antibacterial agents targeting DNA gyrase, an essential enzyme across bacterial species and inhibition results in the disruption of DNA synthesis and subsequently, cell death. The optimization of biochemical activity and other drug-like properties through substitutions to the pyrrole, piperidine, and heterocycle portions of the molecule resulted in pyrrolamides with improved cellular activity and in vivo efficacy.

MeSH terms

  • Amides / chemical synthesis
  • Amides / chemistry*
  • Amides / pharmacology
  • Anti-Bacterial Agents / chemical synthesis
  • Anti-Bacterial Agents / chemistry*
  • Anti-Bacterial Agents / pharmacology*
  • Bacteria / drug effects
  • Binding Sites
  • Crystallography, X-Ray
  • DNA Gyrase / metabolism
  • Enzyme Inhibitors / chemical synthesis
  • Enzyme Inhibitors / chemistry*
  • Enzyme Inhibitors / pharmacology*
  • Microbial Sensitivity Tests
  • Protein Structure, Tertiary
  • Pyrroles / chemistry*
  • Structure-Activity Relationship
  • Topoisomerase II Inhibitors*

Substances

  • Amides
  • Anti-Bacterial Agents
  • Enzyme Inhibitors
  • Pyrroles
  • Topoisomerase II Inhibitors
  • DNA Gyrase