Ebselen as a potent covalent inhibitor of New Delhi metallo-β-lactamase (NDM-1)

Chem Commun (Camb). 2015 Jun 11;51(46):9543-6. doi: 10.1039/c5cc02594j.

Abstract

We report the discovery of a promising NDM-1 inhibitor, ebselen, through a cell-based screening approach. Enzymatic kinetic study and ESI-MS analysis suggested that ebselen could bind to NDM-1 by forming a S-Se bond with the Cys(221) residue at the active site, thereby exhibiting a new inhibition mechanism with broad spectrum inhibitory potential.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Ampicillin / pharmacology
  • Anti-Bacterial Agents / pharmacology
  • Azoles / pharmacology*
  • Escherichia coli / drug effects
  • Escherichia coli / genetics
  • Escherichia coli / metabolism
  • Isoindoles
  • Meropenem
  • Microbial Sensitivity Tests
  • Organoselenium Compounds / pharmacology*
  • Thienamycins / pharmacology
  • beta-Lactamase Inhibitors / pharmacology*
  • beta-Lactamases / genetics
  • beta-Lactamases / metabolism*

Substances

  • Anti-Bacterial Agents
  • Azoles
  • Isoindoles
  • Organoselenium Compounds
  • Thienamycins
  • beta-Lactamase Inhibitors
  • ebselen
  • Ampicillin
  • beta-Lactamases
  • beta-lactamase NDM-1
  • Meropenem