Download MendeleySynthesis, biological properties and structural study of new halogenated azolo[4,5-b]pyridines as inhibitors of CK2 kinase.
Chojnacki, K., Lindenblatt, D., Winska, P., Wielechowska, M., Toelzer, C., Niefind, K., Bretner, M.(2021) Bioorg Chem 106: 104502-104502
- PubMed: 33317841
- DOI: https://doi.org/10.1016/j.bioorg.2020.104502
- Primary Citation of Related Structures:
7A1B, 7A1Z, 7A22, 7A2H, 7A49, 7A4B, 7A4C - PubMed Abstract:
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 IC 50 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 CK2α 1-335 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).
Organizational Affiliation:
Faculty of Chemistry, Warsaw University of Technology, Noakowskiego St. 3, 00-664 Warsaw, Poland. Electronic address: [email protected].
