Institute of Biochemistry and Biophysics, Polish Academy of Sciences, Pawińskiego 5a, 02-106, Warsaw, Poland.
Division of Biophysics, Institute of Experimental Physics, University of Warsaw, Pasteura 5, 02-089, Warsaw, Poland.
Sci Rep. 2021 Dec 8;11(1):23701. doi: 10.1038/s41598-021-03136-8.
4,5,6,7-Tetrabromo-1H-benzotriazole is widely used as the reference ATP-competitive inhibitor of protein kinase CK2. Herein, we study its new analogs: 5,6-diiodo- and 5,6-diiodo-4,7-dibromo-1H-benzotriazole. We used biophysical (MST, ITC) and biochemical (enzymatic assay) methods to describe the interactions of halogenated benzotriazoles with the catalytic subunit of human protein kinase CK2 (hCK2α). To trace the biological activity, we measured their cytotoxicity against four reference cancer cell lines and the effect on the mitochondrial inner membrane potential. The results obtained lead to the conclusion that iodinated compounds are an attractive alternative to brominated ones. One of them retains the cytotoxicity against selected cancer cell lines of the reference TBBt with a smaller side effect on mitochondrial activity. Both iodinated compounds are candidate leaders in the further development of CK2 inhibitors.
4,5,6,7-四溴-1H-苯并三唑被广泛用作蛋白激酶 CK2 的参考型 ATP 竞争抑制剂。在此，我们研究其新的类似物：5,6-二碘-和 5,6-二碘-4,7-二溴-1H-苯并三唑。我们使用生物物理（MST、ITC）和生化（酶测定）方法来描述卤代苯并三唑与人类蛋白激酶 CK2（hCK2α）的催化亚基的相互作用。为了追踪生物活性，我们测量了它们对四种参考癌细胞系的细胞毒性以及对线粒体内膜电位的影响。所得结果得出结论，碘代化合物是溴代化合物的有吸引力的替代品。其中一种化合物保留了对参考 TBBt 的选定癌细胞系的细胞毒性，而对线粒体活性的副作用较小。这两种碘代化合物都是进一步开发 CK2 抑制剂的候选先导化合物。
