Structure-Based Drug Design of Small Molecule Peptide Deformylase Inhibitors to Treat Cancer

Molecules. 2016 Mar 23;21(4):396. doi: 10.3390/molecules21040396.


Human peptide deformylase (HsPDF) is an important target for anticancer drug discovery. In view of the limited HsPDF, inhibitors were reported, and high-throughput virtual screening (HTVS) studies based on HsPDF for developing new PDF inhibitors remain to be reported. We reported here on diverse small molecule inhibitors with excellent anticancer activities designed based on HTVS and molecular docking studies using the crystal structure of HsPDF. The compound M7594_0037 exhibited potent anticancer activities against HeLa, A549 and MCF-7 cell lines with IC50s of 35.26, 29.63 and 24.63 μM, respectively. Molecular docking studies suggested that M7594_0037 and its three derivatives could interact with HsPDF by several conserved hydrogen bonds. Moreover, the pharmacokinetic and toxicity properties of M7594_0037 and its derivatives were predicted using the OSIRIS property explorer. Thus, M7594_0037 and its derivatives might represent a promising scaffold for the further development of novel anticancer drugs.

Keywords: anticancer; high-throughput virtual screening; human peptide deformylase; vanillin N-hydroxyacetamide.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amidohydrolases / antagonists & inhibitors
  • Amidohydrolases / chemistry*
  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents / chemistry*
  • Dose-Response Relationship, Drug
  • Enzyme Inhibitors / administration & dosage
  • Enzyme Inhibitors / chemistry
  • HeLa Cells
  • Humans
  • Hydrogen Bonding / drug effects
  • MCF-7 Cells
  • Molecular Docking Simulation
  • Molecular Structure
  • Neoplasms / drug therapy*
  • Small Molecule Libraries / administration & dosage
  • Small Molecule Libraries / chemistry*


  • Antineoplastic Agents
  • Enzyme Inhibitors
  • Small Molecule Libraries
  • Amidohydrolases
  • peptide deformylase