COX-2 as a Therapeutic Target: An in Silico Approach to Indole Alkaloids for Analgesic Discovery

Pain is a complex physiological process that involves the activation of nociceptors and transmission of pain signals to the brain. COX-2 (Cyclooxygenase-2) is an inducible enzyme that plays a key role in the inflammatory process by converting arachidonic acid into prostaglandins, particularly PGE2, which sensitizes nociceptors and leads to pain perception. Inhibiting COX-2 can reduce inflammation and pain, making it a significant target for drug discovery. This study utilizes computational approaches to explore the binding interactions of natural compounds with COX-2 (PDB ID: 4COX) using molecular docking. Ajmalicin forms van der Waals interactions with residues like VAL:116 and hydrogen bonds with ARG:120 and TYR:355, ensuring strong stability in the binding site. Vellosimine and Vellosiminol exhibit similar interaction profiles, primarily engaging hydrophobic and aromatic residues through van der Waals and Pi-alkyl interactions. Vinorine, the focus of the table, binds extensively to COX-2 through van der Waals and Pi-alkyl interactions with residues such as LEU A:531, MET A:522, and PHE A:518, stabilizing its position within the hydrophobic binding pocket. These natural compounds show potential as COX-2 inhibitors, offering avenues for developing new anti-inflammatory agents.