Institut für Pharmazeutische und Medizinische Chemie, Westfälische Wilhelms-Universität Münster, Hittorfstraße 58-62, 48149 Münster, Germany.
Bioorg Med Chem. 2012 Apr 1;20(7):2282-9. doi: 10.1016/j.bmc.2012.02.017. Epub 2012 Feb 13.
Herein we describe the synthesis and properties of indeno[1,2-b]indole derivatives as a novel class of potent inhibitors of the human protein kinase CK2. A set of 19 compounds was obtained using a convenient and straightforward synthesis protocol. The compounds were tested for inhibition of human protein kinase CK2, which was recombinantly expressed in Escherichia coli. New inhibitors with IC(50) in the micro- and sub-micromolar range were identified. Compound 4b (5-isopropyl-7,8-dihydroindeno[1,2-b]indole-9,10(5H,6H)-dione) inhibited human CK2 with an IC(50) of 0.11 μM and did not significantly inhibit 22 other human protein kinases, suggesting selectivity towards CK2. ATP-competitive inhibition by compound 4b was shown and a K(i) of 0.06 μM was determined. Our findings indicate that indeno[1,2-b]indoles are a promising starting point for further development and optimization of human protein kinase CK2 inhibitors.
在这里，我们描述了吲哚并[1,2-b]吲哚衍生物的合成和性质，它们是一类新型的强效人蛋白激酶 CK2 抑制剂。使用方便且直接的合成方案获得了一组 19 种化合物。对重组表达于大肠杆菌中的人蛋白激酶 CK2 对这些化合物进行了抑制测试。鉴定出具有微摩尔和亚微摩尔范围内的 IC50 的新型抑制剂。化合物 4b（5-异丙基-7,8-二氢吲哚并[1,2-b]吲哚-9,10(5H,6H)-二酮）对人 CK2 的抑制作用的 IC50 为 0.11 μM，并且对其他 22 种人蛋白激酶没有明显抑制作用，表明对 CK2 具有选择性。证明了化合物 4b 的 ATP 竞争性抑制作用，并确定了 K(i)为 0.06 μM。我们的研究结果表明，吲哚并[1,2-b]吲哚是进一步开发和优化人蛋白激酶 CK2 抑制剂的有前途的起点。
