کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
1395615 1501132 2014 11 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Synthesis of novel chiral TBBt derivatives with hydroxyl moiety. Studies on inhibition of human protein kinase CK2α and cytotoxicity properties
موضوعات مرتبط
مهندسی و علوم پایه شیمی شیمی آلی
پیش نمایش صفحه اول مقاله
Synthesis of novel chiral TBBt derivatives with hydroxyl moiety. Studies on inhibition of human protein kinase CK2α and cytotoxicity properties
چکیده انگلیسی


• 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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ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: European Journal of Medicinal Chemistry - Volume 84, 12 September 2014, Pages 364–374
نویسندگان
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