Universität zu Köln

Chojnacki, K., Lindenblatt, D., Winska, P., Wielechowska, M., Toelzer, C., Niefind, K. and Bretner, M. (2021). Synthesis, biological properties and structural study of new halogenated azolo [4,5-b]pyridines as inhibitors of CK2 kinase. Bioorganic Chem., 106. SAN DIEGO: ACADEMIC PRESS INC ELSEVIER SCIENCE. ISSN 1090-2120

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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 CK2 alpha, CK2 alpha' and PIM1 kinases was determined. The most active inhibitors were di- and trihalogenated 1H-triazolo [4,5-bl pyridines (4a, 5a and 10a) with IC50 values 2.56, 3.82 and 3.26 mu M respectively for CK2 alpha. 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 CK2 alpha(1-335) with inhibitors 4a, 5a and 10a were obtained. In addition, new protocol was used to obtain high-resolution crystal structures of CK2 alpha'(Cys336Ser) in complex with four inhibitors (4a, 5a, 5b, 10a).

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Chojnacki, K. UNSPECIFIED UNSPECIFIED UNSPECIFIED Lindenblatt, D. UNSPECIFIED UNSPECIFIED UNSPECIFIED Winska, P. UNSPECIFIED UNSPECIFIED UNSPECIFIED Wielechowska, M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Toelzer, C. UNSPECIFIED UNSPECIFIED UNSPECIFIED Niefind, K. UNSPECIFIED UNSPECIFIED UNSPECIFIED Bretner, M. UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-579414
DOI:	10.1016/j.bioorg.2020.104502
Journal or Publication Title:	Bioorganic Chem.
Volume:	106
Date:	2021
Publisher:	ACADEMIC PRESS INC ELSEVIER SCIENCE
Place of Publication:	SAN DIEGO
ISSN:	1090-2120
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language DUAL INHIBITORS; TUMOR-GROWTH; PROTEIN; BINDING; OPTIMIZATION; CK2-ALPHA; POTENT; ATP; FEATURES; SITE Multiple languages Biochemistry & Molecular Biology; Chemistry, Organic Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/57941