Identification of Ellagic acid analogues as potent inhibitor of protein Kinase CK2:A chemopreventive role in oral Cancer.

Rashi Srivastava,Sanjay Mishra,Rolee Sharma,Salman Akthar

doi:10.6026/97320630011021

Rashi Srivastava, Sanjay Mishra + Show 2 more

Open Access

https://doi.org/10.6026/97320630011021

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Journal: Bioinformation	Publication Date: Jan 30, 2015
Citations: 8	License type: cc-by

Affiliation: IFTM University, Integral University

Abstract

Over expression of Protein kinase (CK2) suppresses apoptosis induced by a variety of agents, whereas down-regulation of CK2 sensitizes cells to induction of apoptosis. In this study, we have built quantitative structure activity relationship (QSAR) models, which were trained and tested on experimentally verified 38 enzyme׳s inhibitors having inhibitory value IC50 in µM. These inhibitors were docked at the active site of CK2 (PDB id: 2ZJW) using AutoDock software, which resulted in energy-based descriptors such as binding energy, intermol energy, torsional energy, internal energy and docking energy. For QSAR modeling, Multiple Linear Regression (MLR) model was engendered using energy-based descriptors yielding correlation coefficient r2 of 0.4645. To assess the predictive performance of QSAR models, different cross-validation procedures were adopted. Our results suggests that ligand-receptor binding interactions for CK2 employing QSAR modeling seems to be a promising approach for prediction of IC50 value of a new ligand molecule against CK2.Further, twenty analogues of ellagic acid were docked with CK2 structure. After docking, two compounds CID 46229200 and CID 10003463 had lower docking energy even lower than standard control Ellagic acid with CK2 was selected as potent candidate drugs for Oral cancer. The biological activity of two compounds in terms of IC50 was predicted based on QSAR model, which could be used as a guideline for anticancerous activity of compounds before their synthesis.

Highlights

Casein kinase 2 (CK2) is a highly ubiquitous, essential, and highly pleiotropic protein kinase [1] that has been involved cell growth, proliferation and in suppression of apoptosis in cells
We have identified the ellagic acid analogues, as a novel, potent and selective CK2 inhibitor
The docking results of the known inhibitors with CK2 were shown in Table 2

Summary

Introduction

Casein kinase 2 (CK2) is a highly ubiquitous, essential, and highly pleiotropic protein kinase [1] that has been involved cell growth, proliferation and in suppression of apoptosis in cells. The 3D coordinates of the crystal structure of human CK2 Molecular structure optimization of ligands were carried out alpha complex with ellagic acid (PDB id: 2ZJW) was retrieved using conjugate gradient method Polak-Ribiere until the from Protein Databank (http://www.rcsb.org/) and taken as maximum energy derivative was lower than 0.1kcal/Å mol in the receptor model in flexible docking program.

Results

Conclusion