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

Future Med Chem. 2020 Sep;12(18):1633-1645. doi: 10.4155/fmc-2020-0048. Epub 2020 Sep 7.

Abstract

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 μM) and Ure in living cell (IC50 = 0.27 μM), with the potency being over 600-fold higher than clinical used drug acetohyroxamic acid, respectively. Surface plasmon resonance demonstrated the high affinity (Kd.#x00A0;= 6.32 nM) of b5 to Ure. Conclusion: This work provides a class of novel and promising Ure inhibitors.

Keywords: Helicobacter pylori; N-monosubstituted thiosemicarbazides; Ure inhibitor; molecular docking; surface plasmon resonance.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Bacterial Agents / chemical synthesis
  • Anti-Bacterial Agents / chemistry
  • Anti-Bacterial Agents / pharmacology*
  • Cell Line
  • Helicobacter pylori / cytology
  • Helicobacter pylori / drug effects*
  • Helicobacter pylori / metabolism
  • Humans
  • Microbial Sensitivity Tests
  • Models, Molecular
  • Molecular Structure
  • Semicarbazides / chemical synthesis
  • Semicarbazides / chemistry
  • Semicarbazides / pharmacology*
  • Virulence Factors / antagonists & inhibitors*
  • Virulence Factors / metabolism

Substances

  • Anti-Bacterial Agents
  • Semicarbazides
  • Virulence Factors
  • thiosemicarbazide