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.
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.
Institut für Pharmazeutische und Medizinische Chemie, Westfälische Wilhelms-Universität Münster, Hittorfstrasse 58-62, 48149 Münster, Germany. claas.hundsdoerfer@wwu.de
Claas
C
Hundsdörfer
Hans-Jörg
HJ
Hemmerling
Janina
J
Hamberger
Marc
M
Le Borgne
Patrick
P
Bednarski
Claudia
C
Götz
Frank
F
Totzke
Joachim
J
Jose
D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D047390:Casein Kinase II / Q000037:antagonists & inhibitors*; D045744:Cell Line, Tumor; D006801:Humans; D007192:Indenes / Q000737:chemistry / Q000494:pharmacology*; D045563:Indolequinones / Q000737:chemistry / Q000494:pharmacology*; D007211:Indoles / Q000737:chemistry / Q000494:pharmacology*; D020128:Inhibitory Concentration 50; D047428:Protein Kinase Inhibitors / Q000737:chemistry / Q000494:pharmacology*
C576059:5-benzyl-5H-indeno(1,2-b)indole-6,9,10-trione; C576058:5-isopropyl-5H-indeno(1,2-b)indole-6,9,10-trione; D000970:Antineoplastic Agents; D007192:Indenes; D045563:Indolequinones; D007211:Indoles; D047428:Protein Kinase Inhibitors; D047390:Casein Kinase II