Design, synthesis, molecular docking studies and in vitro screening of ethyl 4-(3-benzoylthioureido) benzoates as urease inhibitors

Bioorg Chem. 2014 Feb:52:1-7. doi: 10.1016/j.bioorg.2013.10.001. Epub 2013 Oct 30.

Abstract

Thioureas are exceptionally versatile building blocks towards the synthesis of wide variety of heterocyclic systems, which also possess extensive range of pharmacological activities. The substituted benzoic acids were converted into corresponding acid chlorides, these acid chlorides were then treated with potassium thiocyanate in acetone and then the reaction mixture was refluxed for 1-2h afford ethyl 4-(3-benzoylthioureido)benzoates thioureas in good yields. All the newly synthesized compounds were evaluated for their urease inhibitory activities and were found to be potent inhibitors of urease enzyme. Compounds 1f and 1g were identified as the most potent urease inhibitors (IC50 0.21 and 0.13 μM, respectively), and was 100-fold more potent than the standard inhibitors. Further molecular docking studies were carried out using the crystal structure of urease to find out the binding mode of the inhibitors with the enzyme.

Keywords: Antioxidant activity; Ethyl 4-(3-benzoylthioureido)benzoates; Molecular docking; Urease inhibition.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antioxidants / chemistry
  • Antioxidants / pharmacology
  • Benzoates / chemistry
  • Benzoates / pharmacology*
  • Canavalia / enzymology
  • Drug Design
  • Drug Evaluation, Preclinical
  • Enzyme Inhibitors / chemical synthesis
  • Enzyme Inhibitors / chemistry*
  • Enzyme Inhibitors / metabolism
  • Enzyme Inhibitors / pharmacology*
  • Inhibitory Concentration 50
  • Molecular Docking Simulation
  • Molecular Structure
  • Structure-Activity Relationship
  • Urease / antagonists & inhibitors*
  • Urease / metabolism

Substances

  • Antioxidants
  • Benzoates
  • Enzyme Inhibitors
  • Urease