Synthesis of novel polybrominated benzimidazole derivatives-potential CK2 inhibitors with anticancer and proapoptotic activity
PBN-AR
Instytucja
Wydział Chemiczny (Politechnika Warszawska)
Informacje podstawowe
Główny język publikacji
en
Czasopismo
Bioorganic & Medicinal Chemistry
ISSN
0968-0896
EISSN
Wydawca
DOI
URL
Rok publikacji
2016
Numer zeszytu
4
Strony od-do
735-741
Numer tomu
24
Identyfikator DOI
Liczba arkuszy
0.5
Słowa kluczowe
en
4,5,6,7-tetrabromo-1H-benzimidazole derivatives; kinase CK2; inhibition; cytotoxicity; apoptosis
Streszczenia
Język
en
Treść
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).
Inne
System-identifier
WUT68d415dda6d049099d16439ba0d5a7c7
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