Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
1395615 | European Journal of Medicinal Chemistry | 2014 | 11 Pages |
•A series of 4,5,6,7-tetrabromo-1H-benzotriazole derivatives were synthesized.•The most potent inhibitor of CK2α was the (R)-enantiomer of 7b (IC50 0.80 μM).•The obtained results were rationalized by means of in silico docking experiments.•Cytotoxicity was assessed in parallel on the human CCRF-CEM and MCF7 cell lines.
The efficient method for the synthesis of novel 4,5,6,7-tetrabromo-1H-benzotriazole (TBBt) derivatives bearing a single stereogenic center has been developed. New compounds with a variety of substituents at the meta- and para-position of the phenyl ring are reported. All of the presented compounds were obtained using classical synthetic methods, such as bromination of benzotriazole, and its subsequent alkylation by monotosylated arylpropane-1,3-diols, which in turn have been synthesized through reduction of the corresponding prochiral β-keto esters, and the selective monotosylation of the primary hydroxyl group. The influence of the new and previously reported N-hydroxyalkyl TBBt derivatives on the activity of human protein kinase CK2α catalytic subunit was examined. The most active were derivatives with N-hydroxyalkyl substituents (IC50 in 0.80–7.35 μM range). A binding mode of (R)-1-(4,5,6,7-tetrabromo-2H-benzotriazol-2-yl)butan-3-ol 7b to hCK2α has been proposed based on in silico docking studies. Additionally, MTT-based cytotoxicity tests demonstrated high activities of novel 1-aryl-3-TBBt-propan-1-ol and 3-TBBt-propan-1,2-diol derivatives against human peripheral blood T lymphoblast (CCRF-CEM), and moderate anti-tumor activities against human breast adenocarcinoma (MCF7) cell lines.
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