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Development of Pharmacophore Model for Indeno[1,2-b]indoles as Human Protein Kinase CK2 Inhibitors and Database Mining
* 1 , 2 , 2 , 3 , 3 , 2 , 1
1  Institut für Pharmazeutische und Medizinische Chemie, PharmaCampus, Westfälische Wilhelms-Universität Münster, Corrensstr. 48, 48149 Münster, Germany
2  Université de Lyon, Université Claude Bernard Lyon 1, Faculté de Pharmacie - ISPB, EA 4446 Bioactive Molecules and Medicinal Chemistry, SFR Santé Lyon-Est CNRS UMS3453 - INSERM US7, 8 Avenue Rockefeller, F-69373, Lyon Cedex 8, France
3  School of Pharmacy, Faculty of helth sciences, University of Estern Finland, 70211, Kuopio

Published: 01 November 2017 by MDPI in 3rd International Electronic Conference on Medicinal Chemistry session ECMC-3

Casein kinase 2 is a ubiquitous kinase protein emerging as a target for the treatment of cancer. Several active CK2 inhibitors have been developed in the last few years; most of them have ATP-competitive type of inhibition. Indenoindoles present a class of natural and synthetic compounds; many of them have different bioactivity. Here we report on the development of a ligand-based pharmacophore on the basis of different active indenoindoles (training set), the pharmacophore model was challenged against small library of indenoindoles (test set), the study was performed using MOE software. Our model demonstrates good performance in the test set, 85% of the medium or high inhibitory activity compounds were identified, while only 17% of the low or no inhibitory activity compounds were misclassified. Several structures were suggested as possible active CK2 inhibitors by using this model as a base for search in the ZINC database among them was bikaverin which was then further studied.

Keywords: CK2, cancer, pharmacophore, MOE, ZINC database