Developing potential Helicobacter pylori urease inhibitors from novel oxoindoline derivatives: Synthesis, biological evaluation and in silico study

Bioorg Med Chem Lett. 2018 Oct 15;28(19):3182-3186. doi: 10.1016/j.bmcl.2018.08.025. Epub 2018 Aug 25.

Abstract

By recruiting the important moiety from Shikonin, a series of novel oxoindoline derivatives S1-S20 have been synthesized for inhibiting H. pylori urease. The most potent compound S18 displayed better activity (IC50 = 0.71 μM; MIC = 0.48 μM) than the positive controls AHA (IC50 = 17.2 μM) and Metronidazole (MIC = 31.3 μM). With low cytotoxicity, it showed considerable potential for further development. Docking simulation revealed the possible binding pattern of this series. 3D QSAR model was built to discuss SAR and give useful hints for future modification.

Keywords: 3D QSAR; Antimicrobial; Helicobacter pylori; Molecular docking; Oxoindoline derivatives; Urease.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Bacterial Agents / chemical synthesis
  • Anti-Bacterial Agents / chemistry
  • Anti-Bacterial Agents / pharmacology
  • Computer Simulation
  • Drug Development*
  • Enzyme Inhibitors / chemical synthesis*
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / pharmacology*
  • Helicobacter pylori / drug effects
  • Helicobacter pylori / enzymology*
  • Indoles / chemical synthesis*
  • Indoles / chemistry
  • Indoles / pharmacology*
  • Inhibitory Concentration 50
  • Molecular Docking Simulation
  • Quantitative Structure-Activity Relationship
  • Urease / antagonists & inhibitors*

Substances

  • Anti-Bacterial Agents
  • Enzyme Inhibitors
  • Indoles
  • Urease