Chemo-Informatics Evaluation and Invitro Bioactivity Mesurment of Human Cox2 Enzyme Inhibitors Ligands

Cox2 selective inhibitors such as celecoxib, rofecoxib and valdecoxib are recently used to reduce inflammatory response. There is still a need to develop more potent Cox2 inhibitors. This study was conducted to introduce new structures with more affinity to Cox2 enzyme. Chemical structures with 80% similarity to celecoxib was collected by using PubChem at NCBI database. The PDB file of Cox2 enzyme (6COX) obtained from RCSB PDB website in bounding with ligand SC-558 as reference ligand. Docking of ligands to SC-558 site of Cox2 performed with lead IT software (version 2.1.0 BioSolveIT, GmbH, Germany) and the interaction energy of different compounds was obtained. IC50 value of selected compounds identified by using in vitro screening against Cox2 enzyme. The cytotoxicity assay was performed by using MTT method. Screening results in PubChem database was 5000 molecules similar to celecoxib. 24 compounds had better energy scores than 6COX bound co-crystallized ligand SC-558.The ligands were docked with the binding pocket that they showed interaction with Leu352, Phe518,Met522, Val523, Ala527 and Ser353. By visual inspection, compounds showed orientation and hybrid mode similar to SC-558. Discussion & our findings strengthened the computational procedure the discovery of new compounds with anti-inflammatory activity and less toxicity than Cox2 general inhibitors.