Synthesis, biological evaluation, and molecular docking studies of 2,5-substituted-1,4-benzoquinone as novel urease inhibitors

Bioorg Med Chem. 2012 Aug 15;20(16):4889-94. doi: 10.1016/j.bmc.2012.07.002. Epub 2012 Jul 10.

Abstract

A series of 2,5-substituted-1,4-benzoquinone (1-6) were prepared and structurally characterized by elemental analysis, IR spectra, (1)H and (13)C NMR spectra, and single crystal X-ray determination. The urease inhibitory activities of the compounds against H. pylori urease were studied. Among the compounds, 2,5-bis(2-morpholin-4-ylethylamino)-[1,4]benzoquinone (2) shows the most effective activity with IC(50) value of 27.30 ± 2.17 μM. Docking simulation was performed to insert compound 2 into the crystal structure of H. pylori urease at the active site to determine the probable binding mode. As a result, compound 2 may be used as a potential urease inhibitor.

Publication types

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

MeSH terms

  • Benzoquinones / chemistry*
  • Benzoquinones / pharmacology*
  • Crystallography, X-Ray
  • Dose-Response Relationship, Drug
  • Enzyme Inhibitors / chemical synthesis*
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / pharmacology*
  • Helicobacter pylori / enzymology
  • Models, Molecular
  • Molecular Structure
  • Structure-Activity Relationship
  • Urease / antagonists & inhibitors*
  • Urease / metabolism

Substances

  • Benzoquinones
  • Enzyme Inhibitors
  • quinone
  • Urease