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Keywords:

  • molecular dynamic simulation;
  • vascular endothelial growth factor receptor 2 inhibitors;
  • virtual screening

A virtual screening approach was performed to develop novel and potent vascular endothelial growth factor receptor 2 inhibitors. The Specs database was filtered by ‘rule of five’, a pharmacophore model, and docking filter. Sixteen molecules were selected for tube formation assay, a naphthalenol group containing molecule, 12, showed good performance in the study. In the following aortic ring assay and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, 12 was discovered to efficiently inhibit angiogenesis and tumor cell growth. It is the first time to discover naphthalenol scaffold as potent vascular endothelial growth factor receptor 2 inhibitors. Thus, a molecular dynamic simulation process was applied to discover key features of 12 in binding to vascular endothelial growth factor receptor 2. Hydrophobic interactions were discovered to play significant role in the ligand–receptor binding.