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

Abstract

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 (FC / IBC / DDTB)
Edyta Łukowska-Chojnacka,,
- 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
, Martyna Poprzeczko (FC / IBC / DDTB)
Martyna Poprzeczko,,
- Department Of Drug Technology And Biotechnology
, Maria Bretner (FC / IBC / DDTB)
Maria Bretner,,
- Department Of Drug Technology And Biotechnology
Journal seriesBioorganic & Medicinal Chemistry, ISSN 0968-0896, (A 30 pkt)
Issue year2016
Vol24
No4
Pages735-741
Publication size in sheets0.5
Keywords in English4,5,6,7-tetrabromo-1H-benzimidazole derivatives; kinase CK2; inhibition; cytotoxicity; apoptosis
ASJC Classification1605 Organic Chemistry; 1308 Clinical Biochemistry; 3002 Drug Discovery; 3003 Pharmaceutical Science; 1312 Molecular Biology; 1313 Molecular Medicine; 1303 Biochemistry
DOIDOI:10.1016/j.bmc.2015.12.041
URL http://dx.doi.org/10.1016/j.bmc.2015.12.041
Languageen angielski
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wdpb_publikacje_pliki_plik_publikacja_2692_org.pdf 646.55 KB
Score (nominal)30
ScoreMinisterial score = 25.0, 10-09-2019, ArticleFromJournal
Ministerial score (2013-2016) = 30.0, 10-09-2019, ArticleFromJournal
Publication indicators WoS Citations = 14; Scopus Citations = 17; Scopus SNIP (Source Normalised Impact per Paper): 2016 = 0.969; WoS Impact Factor: 2016 = 2.93 (2) - 2016=2.88 (5)
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