Identification of bromophenol thiohydantoin as an inhibitor of DisA, a c-di-AMP synthase, from a 1000 compound library, using the coralyne assay

Chem Commun (Camb). 2014 Oct 4;50(76):11234-7. doi: 10.1039/c4cc02916j.

Abstract

c-di-AMP is an important bacterial second messenger found in Gram-positive and mycobacteria. c-di-AMP regulates myriads of processes in bacteria as well as immune response in higher organisms so interest in small molecules that would attenuate the activity of c-di-AMP metabolism enzymes is high. Herein, we report the first small molecule inhibitor of a c-di-AMP synthase, DisA, using a coralyne-based assay.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Berberine Alkaloids / analysis
  • Berberine Alkaloids / chemistry*
  • Dinucleoside Phosphates / biosynthesis*
  • Dose-Response Relationship, Drug
  • Enzyme Assays*
  • Enzyme Inhibitors / chemical synthesis
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / isolation & purification
  • Enzyme Inhibitors / pharmacology*
  • Molecular Structure
  • Nucleotidyltransferases / antagonists & inhibitors*
  • Nucleotidyltransferases / metabolism
  • Phenols / chemical synthesis
  • Phenols / chemistry
  • Phenols / pharmacology*
  • Small Molecule Libraries / chemical synthesis
  • Small Molecule Libraries / chemistry
  • Small Molecule Libraries / pharmacology*
  • Structure-Activity Relationship

Substances

  • Berberine Alkaloids
  • Dinucleoside Phosphates
  • Enzyme Inhibitors
  • Phenols
  • Small Molecule Libraries
  • cyclic diadenosine phosphate
  • coralyne
  • Nucleotidyltransferases
  • 4-bromophenol