Discovery of a 1,2-bis(3-indolyl)ethane that selectively inhibits the pyruvate kinase of methicillin-resistant Staphylococcus aureus over human isoforms

Bioorg Med Chem Lett. 2014 Nov 1;24(21):5059-62. doi: 10.1016/j.bmcl.2014.09.010. Epub 2014 Sep 16.

Abstract

Methicillin-resistant Staphylococcus aureus pyruvate kinase (MRSA PK) has recently been identified as a target for development of novel antibacterial agents. Testing a series of 1,2-bis(3-indolyl)ethanes against MRSA PK has led to the discovery of a potent inhibitor that is selective over human isoforms.

Keywords: Antibacterial; Indole; MRSA; Pyruvate kinase.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Bacterial Agents / chemistry*
  • Anti-Bacterial Agents / metabolism
  • Anti-Bacterial Agents / pharmacology
  • Drug Evaluation, Preclinical
  • Enzyme Inhibitors / chemistry*
  • Enzyme Inhibitors / metabolism
  • Enzyme Inhibitors / pharmacology
  • Ethane / chemistry*
  • Ethane / metabolism
  • Ethane / pharmacology
  • Humans
  • Indoles / chemistry
  • Methicillin-Resistant Staphylococcus aureus / drug effects
  • Protein Binding
  • Protein Isoforms / antagonists & inhibitors
  • Protein Isoforms / metabolism
  • Pyruvate Kinase / antagonists & inhibitors*
  • Pyruvate Kinase / metabolism

Substances

  • Anti-Bacterial Agents
  • Enzyme Inhibitors
  • Indoles
  • Protein Isoforms
  • indole
  • Pyruvate Kinase
  • Ethane