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.

Abstract

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 IC(50) of 0.18 μM.

• Authors: Claas Hundsdörfer, Hans-Jörg Hemmerling, Janina Hamberger, Marc Le Borgne, Patrick Bednarski, Claudia Götz, Frank Totzke, Joachim Jose
• Journal: Biochemical and biophysical research communications (Biochem Biophys Res Commun) Vol. 424 Issue 1 Pg. 71-5 (Jul 20 2012) ISSN: 1090-2104 [Electronic] United States
• PMID: 22728884 (Publication Type: Journal Article)
• Copyright: Copyright © 2012 Elsevier Inc. All rights reserved.

Chemical References

• 5-benzyl-5H-indeno(1,2-b)indole-6,9,10-trione
• 5-isopropyl-5H-indeno(1,2-b)indole-6,9,10-trione
• Antineoplastic Agents
• Indenes
• Indolequinones
• Indoles
• Protein Kinase Inhibitors
• Casein Kinase II

Topics

• Antineoplastic Agents (chemistry, pharmacology)
• Casein Kinase II (antagonists & inhibitors)
• Cell Line, Tumor
• Humans
• Indenes (chemistry, pharmacology)
• Indolequinones (chemistry, pharmacology)
• Indoles (chemistry, pharmacology)
• Inhibitory Concentration 50
• Protein Kinase Inhibitors (chemistry, pharmacology)