N-monosubstituted thiosemicarbazide as novel Ure inhibitors: synthesis, biological evaluation and molecular docking

Background: Identification of novel Ure inhibitors with high potency has received considerable attention. Methodology/results: Ure inhibition was determined using the indophenol method, the affinities to Ure were estimated via surface plasmon resonance. Seventeen new plus ten known N-monosubstituted thiosemicarbazides were synthesized and identified as novel Ure inhibitors. Out of these compounds, compound b5 shows excellent activity against both crude Ure from Helicobacter pylori (IC50 = 0.04 mu M) and Ure in living cell (IC50 = 0.27 mu M), with the potency being over 600-fold higher than clinical used drug acetohyroxamic acid, respectively. Surface plasmon resonance demonstrated the high affinity (K-d = 6.32 nM) of b5 to Ure. Conclusion: This work provides a class of novel and promising Ure inhibitors.