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The interaction of human CK2α with a series of tetrabromobenzotriazole (TBBt) and tetrabromobenzimidazole (TBBz) analogs, in which one of the bromine atoms proximal to the triazole/imidazole ring is replaced by a methyl group, was studied by biochemical (IC50) and biophysical methods (thermal stability of protein-ligand complex monitored by DSC and fluorescence). Two newly synthesized tri-bromo derivatives display inhibitory activity comparable to that of the reference compounds, TBBt and TBBz, respectively. DSC analysis of the stability of protein-ligand complexes shows that the heat of ligand binding (Hbind) is driven by intermolecular electrostatic interactions involving the triazole/imidazole ring, as indicated by a strong correlation between Hbind and ligand pKa. Screening, based on fluorescence-monitored thermal unfolding of protein-ligand complexes, gave comparable results, clearly identifying ligands that most strongly bind to the protein. Overall results, additionally supported by molecular modeling, confirm that a balance of hydrophobic and electrostatic interactions contribute predominantly, relative to possible intermolecular halogen bonding, in binding of the ligands to the CK2α ATP-binding site.

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A simple and efficient procedure for the synthesis of new optically active imidazolium and triazolium ionic liquids in a three step reaction sequence is described. In the first step, the ring opening of 1,2‐butylene oxide by imidazole or 1,2,4‐triazole resulted in the formation of N‐2‐hydroxybutylimidazole and N‐2‐hydroxybutyl‐1,2,4‐triazole, respectively. In the second step, racemic mixtures of the secondary alcohols were resolved with good enantioselectivity by a lipase‐catalyzed transesterification with enol esters (vinyl acetate and 1‐acetoxy‐2‐methylcyclohexene). In the final step, the optically active intermediates were alkylated with several haloalkanes to yield optically active ionic liquids. The inhibitory activity of the synthesized ionic liquids was tested towards gram‐negative and gram‐positive bacteria and fungi.

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A series of new benzimidazole and benzotriazole derivatives containing a tetrazole moiety was synthesized by N-alkylation of 5-aryltetrazole with 4,5,6,7-tetrabromo-1-(3-chloropropyl)-1H-benzimidazole and 4,5,6,7-tetrabromo-2-(3-chloropropyl)-2H-benzotriazole. The reaction was regioselective and mostly 2,5-disubstituted tetrazole derivatives were obtained. The effect of all synthesized compounds on human recombinant casein kinase 2alpha subunit (rhCK2α) and cytotoxicity against human T-cell lymphoblast (CCRF-CEM) and breast adenocarcinoma (MCF-7) cell lines were evaluated. The results have shown that many of the synthesized compounds exhibit significant cytotoxicity at micromolar concentration.Graphical abstract