Flavone inspired discovery of benzylidenebenzofuran-3(2H)-ones (aurones) as potent inhibitors of human protein kinase CK2

Bioorg Chem. 2020 Sep:102:104062. doi: 10.1016/j.bioorg.2020.104062. Epub 2020 Jun 30.

Abstract

In this work, we describe the design, synthesis and SAR studies of 2-benzylidenebenzofuran-3-ones (aurones), a new family of potent inhibitors of CK2. A series of aurones have been synthesized. These compounds are structurally related to the synthetic flavones and showed nanomolar activities towards CK2. Biochemical tests revealed that 20 newly synthesized compounds inhibited CK2 with IC50 values in the nanomolar range. Further property-based optimization of aurones was performed, yielding a series of CK2 inhibitors with enhanced lipophilic efficiency. The most potent compound 12m (BFO13) has CLipE = 4.94 (CLogP = 3.5; IC50 = 3.6 nM) commensurable with the best known inhibitors of CK2.

Keywords: 2-benzylidenebenzofuran-3-ones; Aurone; In vitro biochemical assay; Molecular docking; Protein kinase CK2 inhibitor; Virtual screening.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Benzofurans / pharmacology
  • Benzofurans / therapeutic use*
  • Casein Kinase II / chemistry
  • Flavones / pharmacology
  • Flavones / therapeutic use*
  • Humans
  • Molecular Docking Simulation / methods*
  • Structure-Activity Relationship

Substances

  • Benzofurans
  • Flavones
  • aurone
  • CSNK2A1 protein, human
  • Casein Kinase II