MOLECULAR DOCKING STUDY OF IBUPROFEN DERIVATIVES AS SELECTIVE INHIBITORS OF CYCLOOXYGENASE-2

The inhibition of the protein cyclooxygenase (COX) is a well-known mechanism for achieving analgesia. Selective inhibitors of cyclooxygenase-2 (COX-2) provide excellent analgesia but can have side-effects. In this study, we chose ibuprofen, a non-selective COX inhibitor that has been safely used for a long time, to develop a novel, selective COX-2 inhibitor. The 3-dimensional structure of the drug target, COX-2, was obtained from the RCSB PDB online database and was input in SeeSAR. Three hundred and thirty alterations were made to ibuprofen molecule. Initial docking was performed in SeeSAR and CLC Drug Discovery Workbench to get a docking score. The 216 ligands that bound to COX-2 with the best binding score were then docked to cyclooxygenase-1 protein (COX-1), and a score was generated based on the binding affinity. Twenty-six of these molecules that didn’t bind to COX-1 were chosen as the selective inhibitors of COX-2 and these were tested for drug-likeness properties using the DruLiTo software. Twenty-two compounds with good drug-likeness properties were subjected to ADMET verification. 5 compounds with good ADMET properties were then subjected to a slower but extremely accurate binding energy test using the AUTODOCK VINA software. The ligand (2S)‐2‐[4‐(2‐oxo‐2, 5‐dihydro-furan‐3‐yl)‐3‐(pyridin‐4‐yl) phenyl] propanoic acid was chosen as the best selective inhibitor of COX-2 that could be derived from Ibuprofen base structure and could be a potential drug compound that can be further tested for effective treatment of pain.