title: Tetraiodobenzimidazoles are potent inhibitors of protein kinase CK2.
abstract: 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.
authors.affiliation: Department of Biological Chemistry and CNR Institute of Neurosciences, University of Padova, viale G. Colombo 3, 35-121 Padova, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Gianoncelli
authors.forename: Giorgio
authors.initials: G
authors.lastname: Cozza
authors.forename: Andrzej
authors.initials: A
authors.lastname: Orzeszko
authors.forename: Flavio
authors.initials: F
authors.lastname: Meggio
authors.forename: Zygmunt
authors.initials: Z
authors.lastname: Kazimierczuk
authors.forename: Lorenzo A
authors.initials: LA
authors.lastname: Pinna
mesh_terms: 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
chemical_list: D001562:Benzimidazoles; D047428:Protein Kinase Inhibitors; D047390:Casein Kinase II