title: Synthesis, Biological Evaluation and Molecular Modeling of Substituted Indeno[1,2-b]indoles as Inhibitors of Human Protein Kinase CK2.
abstract: Due to their system of annulated 6-5-5-6-membered rings, indenoindoles have sparked great interest for the design of ATP-competitive inhibitors of human CK2. In the present study, we prepared twenty-one indeno[1,2-b]indole derivatives, all of which were tested in vitro on human CK2. The indenoindolones 5a and 5b inhibited human CK2 with an IC50 of 0.17 and 0.61 µM, respectively. The indeno[1,2-b]indoloquinone 7a also showed inhibitory activity on CK2 at a submicromolar range (IC50 = 0.43 µM). Additionally, a large number of indenoindole derivatives was evaluated for their cytotoxic activities against the cell lines 3T3, WI-38, HEK293T and MEF.
authors.affiliation: EA 4446 Biomolécules Cancer et Chimiorésistances, SFR Santé Lyon-Est CNRS UMS3453 - INSERM US7, Faculté de Pharmacie - ISPB, Université Lyon 1, 8 avenue Rockefeller, F-69373, Lyon Cedex 8, France. fatenalchab@yahoo.com.
authors.forename: Faten
authors.initials: F
authors.lastname: Alchab
authors.affiliation: EA 4446 Biomolécules Cancer et Chimiorésistances, SFR Santé Lyon-Est CNRS UMS3453 - INSERM US7, Faculté de Pharmacie - ISPB, Université Lyon 1, 8 avenue Rockefeller, F-69373, Lyon Cedex 8, France. laurent.ettouati@univ-lyon1.fr.
authors.forename: Laurent
authors.initials: L
authors.lastname: Ettouati
authors.affiliation: EA 4446 Biomolécules Cancer et Chimiorésistances, SFR Santé Lyon-Est CNRS UMS3453 - INSERM US7, Faculté de Pharmacie - ISPB, Université Lyon 1, 8 avenue Rockefeller, F-69373, Lyon Cedex 8, France. zouhair.bouaziz@univ-lyon1.fr.
authors.forename: Zouhair
authors.initials: Z
authors.lastname: Bouaziz
authors.affiliation: Institut für Pharmazeutische und Medizinische Chemie, PharmaCampus, Westfälische Wilhelms-Universität Münster, Corrensstr. 48, 48149 Münster, Germany. andre.bo@uni-muenster.de.
authors.forename: Andre
authors.initials: A
authors.lastname: Bollacke
authors.affiliation: Laboratoire Récepteurs à dépendance, UMR INSERM U1052/CNRS 5286, Centre de Recherche en Cancérologie de Lyon, Centre Léon Bérard, Cheney A, 28 rue Laënnec, F-69008, Lyon, France. jean-guy.delcros@lyon.unicancer.fr.
authors.forename: Jean-Guy
authors.initials: JG
authors.lastname: Delcros
authors.affiliation: Institut für Pharmazeutische und Medizinische Chemie, Heinrich-Heine-Universität Düsseldorf, Universitätsstr. 1, 40225 Düsseldorf, Germany. christoph.gertzen@uni-duesseldorf.de.
authors.forename: Christoph G W
authors.initials: CG
authors.lastname: Gertzen
authors.affiliation: Institut für Pharmazeutische und Medizinische Chemie, Heinrich-Heine-Universität Düsseldorf, Universitätsstr. 1, 40225 Düsseldorf, Germany. gohlke@uni-duesseldorf.de.
authors.forename: Holger
authors.initials: H
authors.lastname: Gohlke
authors.affiliation: ISM - CNRS UMR 5255, Université de Bordeaux, 351 cours de la Libération, F-33405 Talence cedex, France. noel.pinaud@u-bordeaux.fr.
authors.forename: Noël
authors.initials: N
authors.lastname: Pinaud
authors.affiliation: ICMCB, UPR 9048, CNRS, Université de Bordeaux, 87, avenue du Docteur Schweitzer, F-33600 Pessac, France. mathieu.marchivie@u-bordeaux.fr.
authors.forename: Mathieu
authors.initials: M
authors.lastname: Marchivie
authors.affiliation: Laboratoire ARNA, INSERM U869, UFR des Sciences Pharmaceutiques, Université de Bordeaux, 146 rue Léo Saignat, F-33076 Bordeaux cedex, France. jean.guillon@u-bordeaux.fr.
authors.forename: Jean
authors.initials: J
authors.lastname: Guillon
authors.affiliation: Centre Commun de RMN, Université de Lyon, F-69003 Lyon, France. bernard.fenet@univ-lyon1.fr.|ESCPE Lyon, Université Lyon 1, 43 Bd du 11 Novembre 1918, F-69616 Villeurbanne Cedex, France. bernard.fenet@univ-lyon1.fr.
authors.forename: Bernard
authors.initials: B
authors.lastname: Fenet
authors.affiliation: Institut für Pharmazeutische und Medizinische Chemie, PharmaCampus, Westfälische Wilhelms-Universität Münster, Corrensstr. 48, 48149 Münster, Germany. joachim.jose@uni-muenster.de.
authors.forename: Joachim
authors.initials: J
authors.lastname: Jose
authors.affiliation: EA 4446 Biomolécules Cancer et Chimiorésistances, SFR Santé Lyon-Est CNRS UMS3453 - INSERM US7, Faculté de Pharmacie - ISPB, Université Lyon 1, 8 avenue Rockefeller, F-69373, Lyon Cedex 8, France. marc.le-borgne@univ-lyon1.fr.
authors.forename: Marc Le
authors.initials: ML
authors.lastname: Borgne
keywords: cytotoxicity; indeno[1,2-b]indoles; inhibitory activity; molecular modeling; protein kinase CK2; synthesis