Synthesis of β-Ketosulfone Derivatives As New Non-Cytotoxic Urease Inhibitors In Vitro

Med Chem. 2020;16(2):244-255. doi: 10.2174/1573406415666190415163309.

Abstract

Background: Peptic ulcer and urolithiasis are largely due to infection caused by ureaseproducing bacteria. Therefore, the discovery of urease inhibitors is an important area of medicinal chemistry research.

Objective: The main aim of the work was to identify novel urease inhibitors with no cytotoxicity.

Methods: During the current study, a series of β-ketosulfones 1-26 was synthesized in two steps and evaluated for their in vitro urease inhibition potential.

Results: Out of twenty-six compounds, seventeen have shown good to significant urease inhibitory activity with IC50 values ranging between 49.93-351.46 µM, in comparison to standard thiourea (IC50 = 21 ± 0.11 µM). Moreover, all compounds found to be non-cytotoxic against normal 3T3 cell line.

Conclusion: This study has identified β-ketosulfones as novel and non-cytotoxic urease inhibitors.

Keywords: H. pylori; Urease inhibitors; non-cytotoxic; peptic ulcer; urolithiasis; β-ketosulfones..

MeSH terms

  • Animals
  • Chemistry Techniques, Synthetic
  • Enzyme Inhibitors / chemical synthesis*
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / pharmacology*
  • Enzyme Inhibitors / toxicity
  • Inhibitory Concentration 50
  • Mice
  • Molecular Docking Simulation
  • NIH 3T3 Cells
  • Protein Conformation
  • Structure-Activity Relationship
  • Sulfones / chemical synthesis*
  • Sulfones / chemistry
  • Sulfones / pharmacology*
  • Sulfones / toxicity
  • Urease / antagonists & inhibitors*
  • Urease / chemistry
  • Urease / metabolism

Substances

  • Enzyme Inhibitors
  • Sulfones
  • Urease