title: Indeno[1,2-b]indole derivatives as a novel class of potent human protein kinase CK2 inhibitors.
abstract: 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.
authors.affiliation: Institut für Pharmazeutische und Medizinische Chemie, Westfälische Wilhelms-Universität Münster, Hittorfstraße 58-62, 48149 Münster, Germany.
authors.forename: Claas
authors.initials: C
authors.lastname: Hundsdörfer
authors.forename: Hans-Jörg
authors.initials: HJ
authors.lastname: Hemmerling
authors.forename: Claudia
authors.initials: C
authors.lastname: Götz
authors.forename: Frank
authors.initials: F
authors.lastname: Totzke
authors.forename: Patrick
authors.initials: P
authors.lastname: Bednarski
authors.forename: Marc
authors.initials: M
authors.lastname: Le Borgne
authors.forename: Joachim
authors.initials: J
authors.lastname: Jose
mesh_terms: D047390:Casein Kinase II / Q000037:antagonists & inhibitors* / Q000378:metabolism; D002463:Cell Membrane Permeability / Q000187:drug effects; D006801:Humans; D007211:Indoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D007700:Kinetics; D047428:Protein Kinase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D013237:Stereoisomerism
chemical_list: D007211:Indoles; D047428:Protein Kinase Inhibitors; C030374:indole; D047390:Casein Kinase II