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

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.

A meta‑analysis and bioinformatics exploration of the diagnostic value and molecular mechanism of miR‑193a‑5p in lung cancer

“…In addition, Rabjerg et al ( 78 ) identified CSNK2A1 as a promising novel prognostic biomarker in clear cell renal carcinoma. Furthermore, CSNK2A1 has also been found to be involved in ovarian cancer ( 79 ), oral cancer ( 80 ), prostate cancer ( 81 , 82 ) and pancreatic cancer ( 83 ). A CK2 inhibitor has been implicated in the apoptosis, migration, and metastasis of lung cancer cells ( 84 – 87 ).…”

Enhanced anticancer activity and oral bioavailability of ellagic acid through encapsulation in biodegradable polymeric nanoparticles

“…9 Many in vitro and in vivo investigations established the promising effects of EA, such as antiproliferative drug to arrest the carcinogenesis, direct killer of cancer cells (antitumorigenic), and inhibitor of angiogenesis and metastasis. [10][11][12][13][14][15][16][17] Nonetheless, its therapeutic effect is associated with selective cytotoxicity to carcinoma cells with no harm to normal healthy cells. [10][11][12] Therapeutically, EA has been proclaimed to be effective in the regression of various kinds of tumors, involving but not limited to lung cancer, colorectal carcinoma, esophageal cancer, metastatic melanoma, hepatocellular carcinoma, tongue cancer, breast cancer, bladder cancer, endometrial carcinoma, and prostate cancer.…”

The Development of CK2 Inhibitors: From Traditional Pharmacology to in Silico Rational Drug Design

“…By exploiting a pool of 38 CK2/inhibitors complexes a QSAR model based on Multiple Linear Regression (MLR) was built in combination with a docking protocol (AutoDock) for the generation of energy-based descriptors. After a cross-validation procedure, 20 analogues of ellagic acid were subjected to the QSAR-Docking approach; intriguingly two compounds were predicted in silico to be more potent than ellagic acid, however these results were not validated in a biochemical assays [ 102 ]. On the other hand, CoMFA and CoMSIA methodologies, based on several CK2 inhibitors, were used in a 3D-QSAR study, generating a statistically solid model; unfortunately, the in silico analysis was not applied for the discovery of novel compounds, but only suggested plausible substitutions in the development of CK2 inhibitors [ 103 ].…”