Synthesis, Antimycobacterial Screening and Ligand-Based Molecular Docking Studies on Novel Pyrrole Derivatives Bearing Pyrazoline, Isoxazole and Phenyl Thiourea Moieties

Eur J Med Chem. 2016 Jan 1;107:133-52. doi: 10.1016/j.ejmech.2015.10.047. Epub 2015 Oct 31.


We report here the synthesis, antibacterial and antitubercular evaluation of 61 novel pyrrolyl derivatives bearing pyrazoline, isoxazole and phenyl thiourea moieties. Molecular docking was carried out on enoyl ACP reductase from Mycobacterium tuberculsosis using Surflex-Dock, which is one of the key enzymes involved in type II fatty acid biosynthetic pathway of Mycobacterium tuberculosis, an attractive target for designing novel antitubercular agents. Docking analysis of the crystal structure of ENR performed using Surflex-Dock in Sybyl-X 2.0 software indicates the occupation of substituted pyrrolyl derivatives into hydrophobic pocket of InhA enzyme. Compounds 9b and 9d exhibited the highest antitubercular activity almost close to isoniazid (0.4 μg/mL) with a MIC value of 0.8 μg/mL. All other compounds showed the good activity with a MIC value of 6.25-100 μg/mL. The compounds were further tested for mammalian cell toxicity using human lung cancer cell-line (A549) and were nontoxic. Some compounds exhibited inhibition activities against InhA.

Keywords: Anti-tubercular activity; Cytotoxicity activity; Enzyme inhibition studies; Pyrrolyl chalcones; Pyrrolyl isoxazoles; Pyrrolyl pyrazolines; Surflex docking.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Bacterial Agents / chemical synthesis
  • Anti-Bacterial Agents / chemistry
  • Anti-Bacterial Agents / pharmacology*
  • Antitubercular Agents / chemical synthesis
  • Antitubercular Agents / chemistry*
  • Antitubercular Agents / pharmacology*
  • Bacterial Proteins / antagonists & inhibitors
  • Chemistry Techniques, Synthetic
  • Drug Evaluation, Preclinical / methods
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / pharmacology
  • Escherichia coli / drug effects
  • Humans
  • Isoxazoles / chemistry
  • Ligands
  • Microbial Sensitivity Tests
  • Molecular Docking Simulation
  • Mycobacterium tuberculosis / drug effects
  • Oxidoreductases / antagonists & inhibitors
  • Pyrroles / chemistry
  • Staphylococcus aureus / drug effects
  • Thiourea / chemistry


  • Anti-Bacterial Agents
  • Antitubercular Agents
  • Bacterial Proteins
  • Enzyme Inhibitors
  • Isoxazoles
  • Ligands
  • Pyrroles
  • Oxidoreductases
  • InhA protein, Mycobacterium
  • Thiourea