Synthesis, Biological Evaluation and Molecular Modeling of Substituted Indeno[1,2-b]indoles as Inhibitors of Human Protein Kinase CK2

Pharmaceuticals

Faten Alchab⁵  Laurent Ettouati⁵  Zouhair Bouaziz⁵  Andre Bollacke⁸  Jean-Guy Delcros⁴  Christoph G.W. Gertzen³  Holger Gohlke³  Noël Pinaud¹  Mathieu Marchivie⁶  Jean Guillon²  Bernard Fenet⁷  Joachim Jose⁸ 

[1] ISM - CNRS UMR 5255, Université de Bordeaux, 351 cours de la Libération, F-33405 Talence cedex, France; E-Mail:;Laboratoire ARNA, INSERM U869, UFR des Sciences Pharmaceutiques, Université de Bordeaux, 146 rue Léo Saignat, F-33076 Bordeaux cedex, France; E-Mail:;Institut für Pharmazeutische und Medizinische Chemie, Heinrich-Heine-Universität Düsseldorf, Universitätsstr. 1, 40225 Düsseldorf, Germany; E-Mails:;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; E-Mail:;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; E-Mails:;ICMCB, UPR 9048, CNRS, Université de Bordeaux, 87, avenue du Docteur Schweitzer, F-33600 Pessac, France; E-Mail:;Centre Commun de RMN, Université de Lyon, F-69003 Lyon, France; E-Mail:;Institut für Pharmazeutische und Medizinische Chemie, PharmaCampus, Westfälische Wilhelms-Universität Münster, Corrensstr. 48, 48149 Münster, Germany; E-Mails:

关键词: indeno[1;    2-b]indoles;    synthesis;    protein kinase CK2;    inhibitory activity;    molecular modeling;    cytotoxicity;   

DOI  :  10.3390/ph8020279

来源: mdpi

【 摘 要 】

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.

【 授权许可】

CC BY   
© 2015 by the authors; licensee MDPI, Basel, Switzerland.