Synthesis of novel polybrominated benzimidazole derivatives—potential CK2 inhibitors with anticancer and proapoptotic activity. Issue 4 (15th February 2016)

• Record Type: Journal Article
• Authors: Łukowska-Chojnacka, Edyta; Wińska, Patrycja; Wielechowska, Monika; Poprzeczko, Martyna; Bretner, Maria
• Is Part Of: Bioorganic & medicinal chemistry. Volume 24:Issue 4(2016)
• Page Start: 735
• Page End: 741
• Publication Date: 2016-02-15
• Subjects: 4, 5, 6, 7-Tetrabromo-1H-benzimidazole derivatives -- Kinase CK2 -- Inhibition -- Cytotoxicity -- Apoptosis; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; Biochemistry -- Periodicals; Chemistry, Clinical -- Periodicals; Chemistry, Organic -- Periodicals; Chimie bio-organique -- Périodiques; Chimie pharmaceutique -- Périodiques; 615.19
• DOI: 10.1016/j.bmc.2015.12.041
• Languages: English
• ISSNs: 0968-0896

Abstract

Graphical abstract: 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-1 H -benzimidazole (TBBi) and 4, 5, 6, 7-tetrabromo-2-methyl-1 H -benzimidazole to acrylonitrile, whilst cyanomethyl, cyanopropyl and cyanobutyl analogs by N-alkylation of 4, 5, 6, 7-tetrabromo-1 H -benzimidazole and 4, 5, 6, 7-tetrabromo-2-methyl-1 H -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-1 H -benzimidazole as a new selective inhibitor of rhCK2 with twenty-fold better proapoptotic activity than parental compound (TBBi).