Synthesis, in vitro antiproliferative activity and kinase profile of new benzimidazole and benzotriazole derivatives
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
2017
Numer zeszytu
Strony od-do
1-10
Numer tomu
72
Identyfikator DOI
Liczba arkuszy
0.5
Słowa kluczowe
en
Anticancer activity
Benzimidazole and benzotriazole derivatives
Protein kinase CK2 inhibitors
Streszczenia
Język
en
Treść
Protein kinase 2 (CK2), a member of the serine/threonine kinase family, has been established as a promising target in anticancer therapy. New derivatives of known CK2 inhibitors 4,5,6,7-tetrabromo-1H-benzimidazole (TBBi) and 4,5,6,7-tetrabromo-1H-benzotriazole (TBBt) bearing azide or substituted triazole groups were synthesized. Their influence on the activity of human recombinant CK2α and cytotoxicity against normal and cancer cell lines were evaluated. TBBi derivatives with triazole substituted with carboxyl substituent (7 and 10) exhibited the most potent inhibitory activity against CK2 with Ki value in the range of 1.96-0.91μM, respectively. New TBBi derivatives 2, 3, 5 and 9 have demonstrated the EC50, in the range of 12-25μM and 13-29μM respectively towards CCRF-CEM and MCF-7 cells. Derivatives TBBi decreased viability of cancer cells more efficiently than BALB cells and the biggest differences were observed for the azide substituted compounds 3 and 5. The effect of the most active compounds on the activity of eight off-target kinases was evaluated. Inhibitory efficiency of CK2-mediated p65 phosphorylation was demonstrated for the TBBi and compound 12.
Inne
System-identifier
WUT19dddb18f06b4fbbb6615c1d6409adc0
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