Targeting methionyl tRNA synthetase: design, synthesis and antibacterial activity against Clostridium difficile of novel 3-biaryl-N-benzylpropan-1-amine derivatives

J Enzyme Inhib Med Chem. 2016 Dec;31(6):1694-7. doi: 10.3109/14756366.2016.1140754. Epub 2016 Feb 22.

Abstract

The synthesis of a series of benzimidazole-N-benzylpropan-1-amines and adenine-N-benzylpropan-1-amines is described. Subsequent evaluation against two strains of the anaerobic bacterium Clostridium difficile was performed with three amine derivatives displaying MIC values of 16 μg/mL. Molecular docking studies of the described amines determined that the amines interact within two active site pockets of C. difficile methionyl tRNA synthetase with methoxy substituents in the benzyl ring and an adenine biaryl moiety resulting in optimal binding interactions.

Keywords: 3-Biaryl-N-benzylpropan-1-amines; Clostridium difficile; MetRS–ligand interactions; methionyl-tRNA synthetase; molecular modelling.

MeSH terms

  • Anti-Bacterial Agents / chemical synthesis*
  • Anti-Bacterial Agents / chemistry
  • Anti-Bacterial Agents / pharmacology*
  • Clostridioides difficile / drug effects*
  • Drug Design
  • Methionine-tRNA Ligase / drug effects*
  • Microbial Sensitivity Tests
  • Models, Molecular
  • Propane / analogs & derivatives*
  • Propane / pharmacology

Substances

  • Anti-Bacterial Agents
  • Methionine-tRNA Ligase
  • Propane