A new family of densely functionalized fused-benzoquinones as potent human protein kinase CK2 inhibitors

Eur J Med Chem. 2018 Jan 20:144:410-423. doi: 10.1016/j.ejmech.2017.12.058. Epub 2017 Dec 18.


A new series of 2-amino-4-phenyl-6-hydroxy-7-alkyl-pyranobenzoquinones was synthesized as ATP-competitive CK2 inhibitors. They were readily synthesized through a three-component Knoevenagel condensation-Michael addition-heterocyclization reaction from aldehydes, malononitrile, and 3-alkyl-2,5-dihydroxybenzoquinones. Some of the synthesized compounds presented interesting inhibitory activity with IC50 values in the submicromolar range. A structure-activity relationship study was carried out and the mode of binding was analysed by docking studies and supported by ATP competition assays.

Keywords: Benzoquinones; CK2.

MeSH terms

  • Benzoquinones / chemical synthesis
  • Benzoquinones / chemistry
  • Benzoquinones / pharmacology*
  • Casein Kinase II / antagonists & inhibitors*
  • Casein Kinase II / metabolism
  • Cell Survival / drug effects
  • Dose-Response Relationship, Drug
  • Humans
  • MCF-7 Cells
  • Molecular Structure
  • Protein Kinase Inhibitors / chemical synthesis
  • Protein Kinase Inhibitors / chemistry
  • Protein Kinase Inhibitors / pharmacology*
  • Structure-Activity Relationship


  • Benzoquinones
  • Protein Kinase Inhibitors
  • Casein Kinase II