Identification of new potent phthalazine derivatives with VEGFR-2 and EGFR kinase inhibitory activity

Eur J Med Chem. 2016 Nov 10;123:191-201. doi: 10.1016/j.ejmech.2016.07.049. Epub 2016 Jul 22.


Efforts to develop new antitumor agents are now directed towards multitarget therapies that are believed to have high potency and low tendency to resistance compared to conventional drugs. Herein, we highlighted the synthesis and antitumor activity of five series of phthalazine-based compounds featuring a variety of bioactive chemical fragments at position 1 of the phthalazine nucleus. The antitumor activity of the target compounds was performed against fourteen cancer cell lines where all compounds were active in the nanomolar level. In addition, the mechanism of action of the target compounds was investigated through an enzymatic inhibitory assay against VEGFR-2 and EGFR kinases, revealing potent and preferential activity toward VEGFR-2. Binding mode of the most active compounds was studied using docking experiment.

Keywords: Cytotoxicity; Docking; EGFR; Phthalazine; VEGFR-2.

MeSH terms

  • Antineoplastic Agents / chemistry*
  • Antineoplastic Agents / pharmacology
  • Cell Line, Tumor
  • ErbB Receptors / antagonists & inhibitors*
  • Humans
  • Molecular Docking Simulation
  • Phthalazines / chemistry
  • Phthalazines / pharmacology*
  • Protein Binding
  • Protein Kinase Inhibitors / chemistry*
  • Protein Kinase Inhibitors / pharmacology
  • Structure-Activity Relationship
  • Vascular Endothelial Growth Factor Receptor-2 / antagonists & inhibitors*


  • Antineoplastic Agents
  • Phthalazines
  • Protein Kinase Inhibitors
  • phthalazine
  • ErbB Receptors
  • Vascular Endothelial Growth Factor Receptor-2