New 2-Phenylthiazoles as Potential Sortase A Inhibitors: Synthesis, Biological Evaluation and Molecular Docking

Molecules. 2017 Oct 27;22(11):1827. doi: 10.3390/molecules22111827.


Sortase A inhibition is a well establish strategy for decreasing bacterial virulence by affecting numerous key processes that control biofilm formation, host cell entry, evasion and suppression of the immune response and acquisition of essential nutrients. A meta-analysis of structures known to act as Sortase A inhibitors provided the starting point for identifying a new potential scaffold. Based on this template a series of new potential Sortase A inhibitors, that contain the 2-phenylthiazole moiety, were synthesized. The physicochemical characterisation confirmed the identity of the proposed structures. Antibacterial activity evaluation showed that the new compounds have a reduced activity against bacterial cell viability. However, the compounds prevent biofilm formation at very low concentrations, especially in the case of E. faecalis. Molecular docking studies performed estimate that this is most likely due to the inhibition of Sortase A. The new compounds could be used as add-on therapies together with known antibacterial agents in order to combat multidrug-resistance enterococcal infections.

Keywords: 2-phenylthiazole; Sortase A inhibitor; anti-biofilm activity; antimicrobial; enteroccocus; thiazole.

MeSH terms

  • Aminoacyltransferases / antagonists & inhibitors
  • Aminoacyltransferases / chemistry*
  • Anti-Bacterial Agents / chemistry
  • Anti-Bacterial Agents / pharmacology
  • Bacterial Proteins / antagonists & inhibitors
  • Bacterial Proteins / chemistry*
  • Biofilms / drug effects
  • Cysteine Endopeptidases / chemistry*
  • Cysteine Proteinase Inhibitors / chemical synthesis
  • Cysteine Proteinase Inhibitors / chemistry*
  • Cysteine Proteinase Inhibitors / pharmacology
  • Microbial Sensitivity Tests
  • Molecular Conformation
  • Molecular Docking Simulation
  • Molecular Dynamics Simulation
  • Staphylococcus aureus / drug effects
  • Structure-Activity Relationship
  • Thiazoles / chemical synthesis
  • Thiazoles / chemistry*
  • Thiazoles / pharmacology


  • Anti-Bacterial Agents
  • Bacterial Proteins
  • Cysteine Proteinase Inhibitors
  • Thiazoles
  • Aminoacyltransferases
  • sortase A
  • Cysteine Endopeptidases