Identification of novel inhibitors of bacterial surface enzyme Staphylococcus aureus Sortase A

Bioorg Med Chem Lett. 2008 Jan 1;18(1):380-5. doi: 10.1016/j.bmcl.2007.10.051. Epub 2007 Oct 18.

Abstract

In-silico virtual screening of bacterial surface enzyme Staphylococcus aureus Sortase A against commercial compound libraries using FlexX software package has led to the identification of novel inhibitors. Inhibition of enzyme catalytic activity was determined by monitoring the steady state cleavage of a model peptide substrate. Preliminary structure activity relationship studies on the lead compound resulted in the identification of compounds with improved activity. The most active compound has an IC50 value of 58 microM against the enzyme.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aminoacyltransferases / antagonists & inhibitors*
  • Anti-Bacterial Agents / chemical synthesis
  • Anti-Bacterial Agents / chemistry*
  • Anti-Bacterial Agents / pharmacology*
  • Bacterial Proteins / antagonists & inhibitors*
  • Cysteine Endopeptidases
  • Cysteine Proteinase Inhibitors / chemical synthesis
  • Cysteine Proteinase Inhibitors / chemistry*
  • Cysteine Proteinase Inhibitors / pharmacology*
  • Fluorescence Resonance Energy Transfer
  • Furans / chemical synthesis
  • Furans / chemistry
  • Furans / pharmacology
  • Inhibitory Concentration 50
  • Microbial Sensitivity Tests
  • Models, Molecular
  • Morpholines / chemical synthesis
  • Morpholines / chemistry
  • Morpholines / pharmacology
  • Staphylococcus aureus / enzymology*
  • Structure-Activity Relationship
  • Thiophenes / chemical synthesis
  • Thiophenes / chemistry
  • Thiophenes / pharmacology

Substances

  • Anti-Bacterial Agents
  • Bacterial Proteins
  • Cysteine Proteinase Inhibitors
  • Furans
  • Morpholines
  • Thiophenes
  • Aminoacyltransferases
  • sortase A
  • Cysteine Endopeptidases