Antioxidant activity and antibacterial evaluation of new thiazolin-4-one derivatives as potential tryptophanyl-tRNA synthetase inhibitors

J Enzyme Inhib Med Chem. 2019 Dec;34(1):898-908. doi: 10.1080/14756366.2019.1596086.

Abstract

The rapid emergence of bacterial resistance to antibiotics currently available for treating infectious diseases requires effective antimicrobial agents with new structural profiles and mechanisms of action. Twenty-three thiazolin-4-one derivatives were evaluated for their antibacterial activity by determining the growth inhibition zone diameter, the minimum inhibitory concentration (MIC), and the minimum bactericidal concentration (MBC), against gram-positive and gram-negative bacteria. Compounds 3a-c, 3e-h, 6b-c and 9a-c expressed better MIC values than moxifloxacin, against Staphylococcus aureus. Compounds 3h and 9b displayed similar effect to indolmycin, a tryptophanyl-tRNA ligase inhibitor. Due to their structural analogy to indolmycin, all compounds were subjected to molecular docking on tryptophanyl-tRNA synthetase. Compounds 3a-e, 6a-e, 8 and 9a-e exhibited better binding affinities towards the target enzymes than indolmycin. The antioxidant potential of the compounds was evaluated by four spectrophotometric methods. Thiazolin-4-ones 3e, 6e and 9e presented better antiradical activity than ascorbic acid, trolox and BHT, used as references.

Keywords: Thiazolin-4-one; antibacterial activity; antioxidant activity; docking; tryptophanyl-tRNA synthetase.

MeSH terms

  • Anti-Bacterial Agents / chemical synthesis
  • Anti-Bacterial Agents / chemistry
  • Anti-Bacterial Agents / pharmacology*
  • Antioxidants / chemical synthesis
  • Antioxidants / chemistry
  • Antioxidants / pharmacology*
  • Biphenyl Compounds / antagonists & inhibitors
  • Dose-Response Relationship, Drug
  • Enzyme Inhibitors / chemical synthesis
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / pharmacology*
  • Gram-Negative Bacteria / drug effects
  • Gram-Positive Bacteria / drug effects
  • Microbial Sensitivity Tests
  • Molecular Conformation
  • Molecular Docking Simulation
  • Picrates / antagonists & inhibitors
  • Structure-Activity Relationship
  • Thiazoles / chemical synthesis
  • Thiazoles / chemistry
  • Thiazoles / pharmacology*
  • Tryptophan-tRNA Ligase / antagonists & inhibitors*
  • Tryptophan-tRNA Ligase / metabolism

Substances

  • Anti-Bacterial Agents
  • Antioxidants
  • Biphenyl Compounds
  • Enzyme Inhibitors
  • Picrates
  • Thiazoles
  • 1,1-diphenyl-2-picrylhydrazyl
  • Tryptophan-tRNA Ligase

Grants and funding

This research was supported by the “Iuliu Haţieganu” University of Medicine and Pharmacy Cluj-Napoca under internal research grant no. 4945/24/2016.