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

Pharmaceuticals

Bernard Fenet¹  Laurent Ettouati²  Marc Le Borgne²  Zouhair Bouaziz²  Faten Alchab²  Mathieu Marchivie³  Noël Pinaud⁴  Christoph G.W. Gertzen⁵  Holger Gohlke⁵  Joachim Jose⁶  Andre Bollacke⁶  Jean Guillon⁷  Jean-Guy Delcros⁸ 

[1]Centre Commun de RMN, Université de Lyon, F-69003 Lyon, France

[2]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

[3]ICMCB, UPR 9048, CNRS, Université de Bordeaux, 87, avenue du Docteur Schweitzer, F-33600 Pessac, France

[4]ISM - CNRS UMR 5255, Université de Bordeaux, 351 cours de la Libération, F-33405 Talence cedex, France

[5]Institut für Pharmazeutische und Medizinische Chemie, Heinrich-Heine-Universität Düsseldorf, Universitätsstr. 1, 40225 Düsseldorf, Germany

[6]Institut für Pharmazeutische und Medizinische Chemie, PharmaCampus, Westfälische Wilhelms-Universität Münster, Corrensstr. 48, 48149 Münster, Germany

[7]Laboratoire ARNA, INSERM U869, UFR des Sciences Pharmaceutiques, Université de Bordeaux, 146 rue Léo Saignat, F-33076 Bordeaux cedex, France

[8]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

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

DOI  :  10.3390/ph8020279

来源: DOAJ

【 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】

Unknown