Biological properties and structural study of new aminoalkyl derivatives of benzimidazole and benzotriazole, dual inhibitors of CK2 and PIM1 kinases
PBN-AR
Instytucja
Wydział Chemiczny (Politechnika Warszawska)
Informacje podstawowe
Główny język publikacji
en
Czasopismo
Bioorganic Chemistry (25pkt w roku publikacji)
ISSN
0045-2068
EISSN
Wydawca
DOI
URL
Rok publikacji
2018
Numer zeszytu
Strony od-do
266-275
Numer tomu
80
Identyfikator DOI
Liczba arkuszy
0.5
Autorzy przekładu
(liczba autorów przekładu: 0)
Słowa kluczowe
en
ATP-competitive inhibitors
Antiproliferative activity
Casein kinase 2 CK2
Protein kinase PIM1
Structural study
Streszczenia
Język
en
Treść
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.
Inne
System-identifier
WUTec40d87579ae404d97d82c0932a2696b
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