Synthesis of potent urease inhibitors based on disulfide scaffold and their molecular docking studies

Bioorg Med Chem. 2015 Nov 15;23(22):7211-8. doi: 10.1016/j.bmc.2015.10.017. Epub 2015 Oct 22.

Abstract

Disulfide analogs (1-20) have been synthesized, characterized by HR-MS, (1)H NMR and (13)C NMR and screened for urease inhibitory potential. All compounds were found to have varied degree of urease inhibitory potential ranging in between 0.4 ± 0.01 and 18.60 ± 1.24 μM when compared with standard inhibitor thiourea with IC50 19.46 ± 1.20 μM. Structure activity relationship has been established. The binding interactions of compounds with enzyme were confirmed through molecular docking. All the synthesized compounds 1-20 are new. Our compounds are cheaply synthesizable with high yield and can further be studied to discovery lead compounds. We further, tested for carbonic anhydrase, PDE1 and butyrylcholinesterase but they show no activity. On the other hand we evaluated all compounds for cytotoxicity they showed no toxicity.

Keywords: Cytotoxicity; Disulfide; Molecular docking; Selectivity; Synthesis; Urease inhibition.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3T3-L1 Cells
  • Animals
  • Binding Sites
  • Cell Line
  • Cell Survival / drug effects
  • Disulfides / chemistry*
  • Enzyme Inhibitors / chemical synthesis*
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / pharmacology
  • Humans
  • Inhibitory Concentration 50
  • Mice
  • Molecular Docking Simulation
  • Protein Binding
  • Protein Structure, Tertiary
  • Urease / antagonists & inhibitors*
  • Urease / metabolism

Substances

  • Disulfides
  • Enzyme Inhibitors
  • Urease