Biological properties and structural study of new aminoalkyl derivatives of benzimidazole and benzotriazole, dual inhibitors of CK2 and PIM1 kinases

Konrad Chojnacki , Patrycja Wińska , Monika Wielechowska , Edyta Łukowska-Chojnacka , C. Tölzer , K. Niefind , Maria Bretner


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 α, 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 α1-335/8b was crystallized, both under high-salt conditions and under low-salt conditions giving crystals which diffracted X-rays to about 2.4 Å resolution, what enabled the determination of the corresponding 3D-structures.
Author Konrad Chojnacki (FC / IBC / DDTB)
Konrad Chojnacki,,
- Department Of Drug Technology And Biotechnology
, Patrycja Wińska (FC / IBC / DDTB)
Patrycja Wińska,,
- Department Of Drug Technology And Biotechnology
, Monika Wielechowska (FC / IBC / DDTB)
Monika Wielechowska,,
- Department Of Drug Technology And Biotechnology
, Edyta Łukowska-Chojnacka (FC / IBC / DDTB)
Edyta Łukowska-Chojnacka,,
- Department Of Drug Technology And Biotechnology
, C. Tölzer
C. Tölzer,,
, K. Niefind
K. Niefind,,
, Maria Bretner (FC / IBC / DDTB)
Maria Bretner,,
- Department Of Drug Technology And Biotechnology
Journal seriesBioorganic Chemistry, ISSN 0045-2068, (A 25 pkt)
Issue year2018
Publication size in sheets0.5
Keywords in EnglishATP-competitive inhibitors; Antiproliferative activity; Casein kinase 2 CK2; Protein kinase PIM1; Structural study
ASJC Classification1605 Organic Chemistry; 3002 Drug Discovery; 1312 Molecular Biology; 1303 Biochemistry
Languageen angielski
1-s2.0-S0045206818302748-main.pdf 811.41 KB
Score (nominal)25
ScoreMinisterial score = 25.0, 21-03-2019, ArticleFromJournal
Ministerial score (2013-2016) = 25.0, 21-03-2019, ArticleFromJournal
Publication indicators WoS Citations = 1; Scopus SNIP (Source Normalised Impact per Paper): 2016 = 1.147; WoS Impact Factor: 2017 = 3.929 (2) - 2017=3.39 (5)
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