Department of Biological Chemistry and CNR Institute of Neurosciences, University of Padova, viale G. Colombo 3, 35-121 Padova, Italy.
Bioorg Med Chem. 2009 Oct 15;17(20):7281-9. doi: 10.1016/j.bmc.2009.08.047. Epub 2009 Aug 27.
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.
一系列新型碘代苯并咪唑类化合物通过在硫酸溶液中用碘和过碘酸碘化相应的苯并咪唑而制备。此外，还获得了几种 4,5,6,7-四碘苯并咪唑（TIBI）的 2-取代和 N-1-羧甲基取代衍生物。为了进行比较，还合成了一些新的 4,5,6,7-四溴苯并咪唑。评估了这些新化合物抑制蛋白激酶 CK2 的能力。结果表明，4,5,6,7-四碘苯并咪唑类化合物比相应的四溴代类似物对 CK2 具有更强的抑制作用。分子模拟支持实验数据，表明四碘苯并咪唑部分比相应的四溴和四氯化合物更能填满结合口袋。值得注意的是，4,5,6,7-四碘苯并咪唑（TIBI）是迄今为止描述的最有效的 CK2 抑制剂之一（K(i)=23 nM）。
