Tetraiodobenzimidazoles are potent inhibitors of protein kinase CK2.
A series of novel iodinated benzimidazoles have been prepared by iodination of respective benzimidazole with iodine and periodic acid in sulfuric acid solution. Additionally several 2-substituted- and N-1-carboxymethyl-substituted derivatives of 4,5,6,7-tetraiodobenzimidazole (TIBI) were obtained. For sake of comparison, some new 4,5,6,7-tetrabromobenzimidazoles were also synthesized. The ability of the new compounds to inhibit protein kinase CK2 has been evaluated. The results show that 4,5,6,7-tetraiodobenzimidazoles are more powerful inhibitors of CK2 than their tetrabrominated analogs. Molecular modeling supports the experimental data showing that tetraiodobenzimidazole moiety fills better the binding pocket than respective tetrabromo and tetrachlorocompounds. To note that 4,5,6,7-tetraiodobenzimidazole (TIBI) is one of the most efficient CK2 inhibitors (K(i)=23 nM) described to date.
Gianoncelli
Alessandra
A
Department of Biological Chemistry and CNR Institute of Neurosciences, University of Padova, viale G. Colombo 3, 35-121 Padova, Italy.
Cozza
Giorgio
G
Orzeszko
Andrzej
A
Meggio
Flavio
F
Kazimierczuk
Zygmunt
Z
Pinna
Lorenzo A
LA
D001562:Benzimidazoles / Q000737:chemistry / Q000494:pharmacology*; D047390:Casein Kinase II / Q000037:antagonists & inhibitors*; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D047428:Protein Kinase Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D013056:Spectrophotometry, Ultraviolet
D001562:Benzimidazoles; D047428:Protein Kinase Inhibitors; D047390:Casein Kinase II