Synthesis, biological activity and structural study of new benzotriazole-based protein kinase CK2 inhibitorsElectronic supplementary information (ESI) available: 1H and 13C NMR spectra of 9, 10, 14-17, 20-22; First Docking studies. See DOI: 10.1039/c5ra12114k

A new series of 4,5,6,7-tetrabromobenzotriazole (TBB) derivatives was synthesized and characterized as CK2 inhibitors. They were readily synthesized using a click chemistry approach based on a Cu( i )-catalyzed azide-alkyne 1,3-dipolar cycloaddition (CuAAC). Some of the synthesized compounds present interesting inhibitory activities using an in vitro assay, with K i values in the low micro molar range and a high degree of selectivity against a panel of 24 kinases. Selected compounds were tested for their antiproliferative effect on several cancer cell lines, and for their proapoptotic activity towards human Jurkat T-leukemia and MCF-7 breast adenocarcinoma cells, showing that they can be proposed as promising anticancer agents. Docking studies as well as crystallographic analysis allowed us to identify ligand-CK2 interactions that account for the molecular recognition process, and can help to further optimize this family of compounds as CK2 inhibitors. A new series of TBB-derivatives was synthesized and characterized as CK2 inhibitors. Crystallographic analysis and docking studies were used to understand the mode of binding.