In silico library design, screening and MD simulation of COX-2 inhibitors for anticancer activity

Abstract

Health problems are increasing worldwide pertaining to cancer modalities. Cyclooxygenase enzyme is known to be involved in cancer biology, neurological disorders, cardiovascular and other diseases. It has been a promising target for developing novel anti-inflammatory drugs in breast cancer treatment. Hence, a computer-aided drug design strategy was applied to identify potent inhibitors of the COX-2 receptor. For this purpose, 12084 ligands from different databases to be tested based on similarity search criteria and were docked against our target protein COX-2 retrieved from the protein data bank. The high-throughput virtual screening protocol was performed and examined the compounds for its binding free energies. Eleven compounds were found out with better binding affinity by virtual screening results and showed interaction with the protein at the known active site. The selected compounds filtered through the Lipinski‟s rule of five. The physicochemical properties and bioactivity scores were calculated. Molecular docking calculations, MD simulations, ADMET properties, and protein-ligand interaction were analyzed to determine the suitability of each ligand. Overall, the results from our study suggest that compound ZINC000039428234 could be a potent inhibitor for the COX-2 protein of breast cancer. We look forward to this result is of the enormous key in designing a potential drug candidate for breast cancer.