New class of competitive inhibitor of bacterial histidine kinases

J Bacteriol. 2005 Dec;187(23):8196-200. doi: 10.1128/JB.187.23.8196-8200.2005.

Abstract

Bacterial histidine kinases have been proposed as targets for the discovery of new antibiotics, yet few specific inhibitors of bacterial histidine kinases have been reported. We report here a novel thienopyridine (TEP) compound that inhibits bacterial histidine kinases competitively with respect to ATP but does not comparably inhibit mammalian serine/threonine kinases. Although it partitions into membranes and does not inhibit the growth of bacterial or mammalian cells, TEP could serve as a starting compound for a new class of histidine kinase inhibitors with antibacterial activity.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bacterial Proteins / drug effects*
  • Bacterial Proteins / metabolism
  • Dose-Response Relationship, Drug
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / pharmacology*
  • Histidine Kinase
  • Protein Kinases / drug effects*
  • Protein Kinases / metabolism
  • Pyridines / chemistry
  • Pyridines / pharmacology*

Substances

  • Bacterial Proteins
  • Enzyme Inhibitors
  • Pyridines
  • thienopyridine
  • Protein Kinases
  • Histidine Kinase