Design, synthesis and biological evaluation of new embelin derivatives as CK2 inhibitors

Bioorg Chem. 2020 Jan:95:103520. doi: 10.1016/j.bioorg.2019.103520. Epub 2019 Dec 18.

Abstract

A new series of furan embelin derivatives was synthesized and characterized as ATP-competitive CK2 inhibitors. The new compounds were efficiently synthesized using a multicomponent approach from embelin (1), aldehydes and isonitriles through a Knoevenagel condensation/Michael addition/heterocyclization. Several compounds with inhibitory activities in the low micromolar or even submicromolar were identified. The most active derivative was compound 4l (2-(tert-butylamino)-3-(furan-3-yl)-5-hydroxy-6-undecylbenzofuran-4,7-dione) with an IC50 value of 0.63 μM. It turned out to be an ATP competitive CK2 inhibitor with a Ki value determined to be 0.48 μM. Docking studies allowed the identification of key ligand-CK2 interactions, which could help to further optimize this family of compounds as CK2 inhibitors.

Keywords: CK2; Docking; Embelin; MCR.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Triphosphate / metabolism
  • Benzoquinones / chemical synthesis
  • Benzoquinones / chemistry*
  • Benzoquinones / pharmacology*
  • Binding, Competitive
  • Casein Kinase II / antagonists & inhibitors*
  • Drug Design*
  • Drug Evaluation, Preclinical
  • Furans / chemistry
  • Humans
  • MCF-7 Cells
  • Molecular Docking Simulation
  • Protein Kinase Inhibitors / chemical synthesis
  • Protein Kinase Inhibitors / chemistry
  • Protein Kinase Inhibitors / pharmacology*
  • Structure-Activity Relationship

Substances

  • Benzoquinones
  • Furans
  • Protein Kinase Inhibitors
  • Adenosine Triphosphate
  • Casein Kinase II
  • embelin
  • furan