Discovery and characterization of aryl isonitriles as a new class of compounds versus methicillin- and vancomycin-resistant Staphylococcus aureus

Eur J Med Chem. 2015 Aug 28:101:384-90. doi: 10.1016/j.ejmech.2015.06.031. Epub 2015 Jun 16.

Abstract

Methicillin- and vancomycin-resistant Staphylococcus aureus (MRSA and VRSA) have emerged as a global health concern. A new class of compounds featuring an aryl isonitrile moiety has been discovered that exhibits potent inhibitory activity against several clinically-relevant MRSA and VRSA isolates. Structure-activity relationship studies have been conducted to identify the aryl isonitrile group as the key functional group responsible for the observed antibacterial activity. The most potent antibacterial aryl isonitrile analogs (MIC 2 μM) did not show any toxicity against mammalian cells up to a concentration of 64 μM.

Keywords: Antibiotic; Drug resistance; Isonitrile; MRSA; VRSA.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Anti-Bacterial Agents / chemical synthesis
  • Anti-Bacterial Agents / chemistry
  • Anti-Bacterial Agents / pharmacology*
  • Caco-2 Cells
  • Cell Line
  • Cell Survival / drug effects
  • Dose-Response Relationship, Drug
  • Drug Discovery*
  • Humans
  • Methicillin Resistance / drug effects*
  • Mice
  • Microbial Sensitivity Tests
  • Molecular Structure
  • Nitriles / chemical synthesis
  • Nitriles / chemistry
  • Nitriles / pharmacology*
  • Staphylococcus aureus / drug effects*
  • Structure-Activity Relationship
  • Vancomycin Resistance / drug effects*

Substances

  • Anti-Bacterial Agents
  • Nitriles