Synthesis of novel polybrominated benzimidazole derivatives-potential CK2 inhibitors with anticancer and proapoptotic activity

Edyta Łukowska-Chojnacka , Patrycja Wińska , Monika Wielechowska , Martyna Poprzeczko , Maria Bretner


The efficient method for the synthesis of novel cell permeable inhibitors of protein kinase CK2 with anticancer and proapoptotic activity has been developed. A series of polybrominated benzimiadazole derivatives substituted by various cyanoalkyl groups have been synthesized. Cyanoethyl derivatives were obtained by Michael type addition of 4,5,6,7-tetrabromo-1H-benzimidazole (TBBi) and 4,5,6,7-tetrabromo-2-methyl-1H-benzimidazole to acrylonitrile, whilst cyanomethyl, cyanopropyl and cyanobutyl analogs by N-alkylation of 4,5,6,7-tetrabromo-1H-benzimidazole and 4,5,6,7-tetrabromo-2-methyl-1H-benzimidazole with appropriate cyanoalkyl halides. The inhibitory activity against protein kinase rhCK2α catalytic subunit and cytotoxicity against two human cancer cell lines: acute lymphocytic leukemia (CCRF-CEM) and breast (MCF-7) were evaluated for all newly synthesized compounds. Additionally, the proapoptotic activity toward leukemia cells and intracellular inhibition of CK2 for the most cytotoxic derivatives have been performed, demonstrating 4,5,6,7-tetrabromo-2-methyl-1H-benzimidazole as a new selective inhibitor of rhCK2 with twenty-fold better proapoptotic activity than parental compound (TBBi).
Author Edyta Łukowska-Chojnacka ZTiBSL
Edyta Łukowska-Chojnacka,,
- Department Of Drug Technology And Biotechnology
, Patrycja Wińska ZTiBSL
Patrycja Wińska,,
- Department Of Drug Technology And Biotechnology
, Monika Wielechowska ZTiBSL
Monika Wielechowska,,
- Department Of Drug Technology And Biotechnology
, Martyna Poprzeczko ZTiBSL
Martyna Poprzeczko,,
- Department Of Drug Technology And Biotechnology
, Maria Bretner ZTiBSL
Maria Bretner,,
- Department Of Drug Technology And Biotechnology
Journal seriesBioorganic & Medicinal Chemistry, ISSN 0968-0896
Issue year2016
Publication size in sheets0.5
Keywords in English4,5,6,7-tetrabromo-1H-benzimidazole derivatives; kinase CK2; inhibition; cytotoxicity; apoptosis
Languageen angielski
wdpb_publikacje_pliki_plik_publikacja_2692_org.pdf 646.55 KB
Score (nominal)30
ScoreMinisterial score = 25.0, 28-11-2017, ArticleFromJournal
Ministerial score (2013-2016) = 30.0, 28-11-2017, ArticleFromJournal
Publication indicators WoS Impact Factor: 2016 = 2.93 (2) - 2016=2.88 (5)
Citation count*0
Share Share

Get link to the record

* presented citation count is obtained through Internet information analysis and it is close to the number calculated by the Publish or Perish system.