Synthesis and evaluation of anticancer activity of new 4,5,6,7-tetrabromo-1H-benzimidazole derivatives.

Autor: Łukowska-Chojnacka E; Faculty of Chemistry, Warsaw University of Technology, Noakowskiego St. 3, 00-664 Warsaw, Poland. Electronic address: edyta.chojnacka@pw.edu.pl., Fedorov E; Faculty of Chemistry, Warsaw University of Technology, Noakowskiego St. 3, 00-664 Warsaw, Poland., Kowalkowska A; Faculty of Chemistry, Warsaw University of Technology, Noakowskiego St. 3, 00-664 Warsaw, Poland., Wielechowska M; Faculty of Chemistry, Warsaw University of Technology, Noakowskiego St. 3, 00-664 Warsaw, Poland., Sobiepanek A; Faculty of Chemistry, Warsaw University of Technology, Noakowskiego St. 3, 00-664 Warsaw, Poland., Koronkiewicz M; Department of Biomedical Research, National Medicines Institute, Chełmska St. 30/34, 00-725 Warsaw, Poland., Wińska P; Faculty of Chemistry, Warsaw University of Technology, Noakowskiego St. 3, 00-664 Warsaw, Poland.
Jazyk: angličtina
Zdroj: Bioorganic chemistry [Bioorg Chem] 2024 Dec; Vol. 153, pp. 107880. Date of Electronic Publication: 2024 Oct 10.
DOI: 10.1016/j.bioorg.2024.107880
Abstrakt: An efficient method for the synthesis of new 4,5,6,7-tetrabromo-1H-benzimidazole derivatives has been developed. New ketones were obtained by N-alkylation of TBBi or 2-Me-TBBi with various phenacyl halides and then reduced to the corresponding alcohols. All compounds were obtained with satisfactory yields in the range of 40-91 %. The synthesized compounds appeared a weak CK2 and PIM-1 inhibitors but exhibit an interesting cytotoxic activity against cancer cell lines, i.e. MCF-7, PC-3, CCRF-CEM, K-562. 1-Phenyl-2-(4,5,6,7-tetrabromo-1H-benzimidazol-1-yl)ethanone 3aA exhibits the highest cytotoxic activity with IC 50 value of 5.30 µM for MCF-7 and 6.80 µM for CCRF-CEM. Moreover, this compound shows the highest selectivity against both MCF-7 and CCRF-CEM with SI selectivity coefficients (against MRC-5 and Vero cells) equal 5.45 and 4.30 for MCF-7 and 4.25 and 3.35 for CCRF-CEM, respectively. Furthermore, it was shown that compound 3aA exhibits very good pro-apoptotic properties, through induction of the mitochondrial apoptotic pathway in CCRF-CEM cells. These results correlate with data showing the effect of 3aA on intracellular level of CK2α protein and CK2-mediated phosphorylation of Ser529 in NF-κBp65. Study of the effect of compound 3aA on mRNA levels of CK2α and CK2α' showed no significant differences in gene expression levels in control CCRF-CEM and cells treated with 3aA, indicating 3aA action at the protein level.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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