Universität zu Köln

Chojnacki, K., Winska, P., Wielechowska, M., Lukowska-Chojnacka, E., Toelzer, C., Niefind, K. and Bretner, M. (2018). Biological properties and structural study of new aminoalkyl derivatives of benzimidazole and benzotriazole, dual inhibitors of CK2 and PIM1 kinases. Bioorganic Chem., 80. S. 266 - 276. SAN DIEGO: ACADEMIC PRESS INC ELSEVIER SCIENCE. ISSN 1090-2120

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Abstract

The new aminoalkyl-substituted derivatives of known CK2 inhibitors 4,5,6,7-tetrabromo-1H-benzimidazole (TBBi) and 4,5,6,7-tetrabromo-1H-benzotriazole (TBBt) were synthesized, and their influence on the activity of recombinant human CK2 alpha, CK2 holoenzyme and PIM1 kinases was evaluated. All derivatives inhibited the activity of studied kinases and the most efficient were aminopropyl-derivatives 8b and 14b. These compounds also exerted inhibition of cancer cell lines - CCRF-CEM (acute lymphoblastoid leukemia), MCF-7 (human breast cancer), and PC-3 (prostate cancer) proliferation and their EC50 is comparable with the value for clinically studied CK2 inhibitor CX-4945. Preliminary structure activity relationship analysis indicated that the spacer length affected antitumor potency, and two to three methylene units were more favorable. The complex of CK2 alpha(1-335)/8b was crystallized, both under high-salt conditions and under low-salt conditions giving crystals which diffracted X-rays to about 2.4 angstrom resolution, what enabled the determination of the corresponding 3D-structures.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Chojnacki, K. UNSPECIFIED UNSPECIFIED UNSPECIFIED Winska, P. UNSPECIFIED UNSPECIFIED UNSPECIFIED Wielechowska, M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Lukowska-Chojnacka, E. UNSPECIFIED UNSPECIFIED UNSPECIFIED Toelzer, C. UNSPECIFIED UNSPECIFIED UNSPECIFIED Niefind, K. UNSPECIFIED UNSPECIFIED UNSPECIFIED Bretner, M. UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-172309
DOI:	10.1016/j.bioorg.2018.06.022
Journal or Publication Title:	Bioorganic Chem.
Volume:	80
Page Range:	S. 266 - 276
Date:	2018
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 FACTOR-KAPPA-B; CATALYTIC SUBUNIT; ANTIPROLIFERATIVE ACTIVITY; PROTEIN; POTENT; FEATURES; RECOGNITION; PROSURVIVAL; PLASTICITY; CK2-ALPHA Multiple languages Biochemistry & Molecular Biology; Chemistry, Organic Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/17230