Synthesis, biological properties and structural study of new halogenated azolo[4,5-b]pyridines as inhibitors of CK2 kinase

Bioorg Chem. 2021 Jan;106:104502. doi: 10.1016/j.bioorg.2020.104502. Epub 2020 Nov 24.


The new halogenated 1H-triazolo[4,5-b]pyridines and 1H-imidazo[4,5-b]pyridines were synthesised as analogues of known CK2 inhibitors: 4,5,6,7-tetrabromo-1H-benzotriazole (TBBt) and 4,5,6,7-tetrabromo-1H-benzimidazole (TBBi). Their influence on the activity of recombinant human CK2α, CK2α' and PIM1 kinases was determined. The most active inhibitors were di- and trihalogenated 1H-triazolo[4,5-b]pyridines (4a, 5a and 10a) with IC50 values 2.56, 3.82 and 3.26 μM respectively for CK2α. Furthermore, effect on viability of cancer cell lines MCF-7 (human breast adenocarcinoma) and CCRF-CEM (T lymphoblast leukemia) of all final compounds was evaluated. Finally, three crystal structures of complexes of CK2α1-335 with inhibitors 4a, 5a and 10a were obtained. In addition, new protocol was used to obtain high-resolution crystal structures of CK2α'Cys336Ser in complex with four inhibitors (4a, 5a, 5b, 10a).

Keywords: ATP-Competitive inhibitors; Casein Kinase CK2; Protein Kinase PIM1; Structural study.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Casein Kinase II / antagonists & inhibitors*
  • Casein Kinase II / metabolism
  • 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


  • Protein Kinase Inhibitors
  • Casein Kinase II