2-(Hetero(aryl)methylene)hydrazine-1-carbothioamides as potent urease inhibitors

Chem Biol Drug Des. 2015 Feb;85(2):225-30. doi: 10.1111/cbdd.12379. Epub 2014 Jul 10.

Abstract

A small series of 2-(hetero(aryl)methylene) hydrazine-1-carbothioamides including two aryl derivatives was synthesized and tested for their inhibitory activity against urease. Compound (E)-2-(Furan-2-ylmethylene) hydrazine-1-carbothioamide (3f), having a furan ring, was the most potent inhibitor of urease with an IC50 value of 0.58 μM. Molecular modeling was carried out through docking the designed compounds into the urease binding site to predict whether these derivatives have analogous binding mode to the urease inhibitors. The study revealed that all of the tested compounds bind with both metal atoms at the active site of the enzyme. The aromatic ring of the compounds forms ionic interactions with the residues, Ala(440), Asp(494), Ala(636), and Met(637).

Keywords: Schiff bases; molecular modeling; thiosemicarbazones; urease inhibitors.

MeSH terms

  • Canavalia / enzymology*
  • Enzyme Inhibitors / chemistry*
  • Enzyme Inhibitors / pharmacology
  • Hydrazines / chemistry*
  • Hydrazines / pharmacology
  • Models, Molecular
  • Structure-Activity Relationship
  • Thioamides / chemistry*
  • Thioamides / pharmacology
  • Urease / antagonists & inhibitors*
  • Urease / metabolism

Substances

  • Enzyme Inhibitors
  • Hydrazines
  • Thioamides
  • hydrazine
  • Urease