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

Bioorganic & Medicinal Chemistry
Edyta Łukowska-ChojnackaMaria 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).

References

May 22, 2008·Advances in Enzyme Regulation·Kashif A AhmadKhalil Ahmed
Jan 27, 2009·Bioorganic & Medicinal Chemistry·Andzelika Najda-BernatowiczMaria Bretner
Apr 20, 2010·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Miriam López-RamosClaude Cochet
Sep 30, 2014·Journal of Molecular and Genetic Medicine : an International Journal of Biomedical Research·Maya AgarwalGordon Li

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Citations

Dec 13, 2016·European Journal of Medicinal Chemistry·Wasim AkhtarM Mumtaz Alam
Mar 24, 2018·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Ling-Xia LiChun-Long Yang
Sep 13, 2018·Zeitschrift Für Naturforschung. C, a Journal of Biosciences·Asmaa A Magd-El-DinAhmed H El-Desoky
Jul 10, 2021·Bioorganic Chemistry·Adel S GirgisAhmed A F Soliman

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