Novel indeno[1,2-b]indoloquinones as inhibitors of the human protein kinase CK2 with antiproliferative activity towards a broad panel of cancer cell lines

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• 作者：Claas Hundsd?rfer ; Hans-J?rg Hemmerling ; Janina Hamberger ; Marc Le Borgne ; Patrick Bednarski ; Claudia G?tz ; Frank Totzke ; Joachim Jose
• 关键词：Inhibitors ; Protein kinase ; CK2 ; Cancer ; ARK5 ; FLT3
• 刊名：Biochemical and Biophysical Research Communications
• 出版年：2012
• 出版时间：20 July, 2012
• 年：2012
• 卷：424
• 期：1
• 页码：71-75
• 全文大小：224 K

文摘

We previously reported indeno[1,2-b]indoles as a novel class of potent inhibitors of the human protein kinase CK2. In the present study we prepared two novel quinoid derivatives, the indeno[1,2-b]indoloquinones 6b and 6c, and demonstrated inhibition of the human CK2 by the compounds. Furthermore, we showed substantial antiproliferative activity of both compounds towards a broad panel of human cancer cell lines in the low micromolar range. Whereas the earlier indeno[1,2-b]indoles have been shown to be selective for CK2, the indeno[1,2-b]indoloquinones 6b and 6c also inhibited the AMPK activated protein kinase ARK5, potentially contributing to the anti-cancer effects of the compounds. In addition, with compound 6b we found a very potent inhibitor of the leukemia-associated receptor tyrosine kinase FLT3, with an IC₅₀ of 0.18 ¦ÌM.