Evaluating the Anti-Cancer Potential of Natural Flavonoids COX-2 Inhibition through Molecular Docking

Abstract The cyclooxygenase-2 (COX-2) receptor is a therapeutic target for the development of potential drugs with anti-inflammatory activity. Rofecoxib, one of the first selective COX-2 inhibitors (coxibs), was approved for use in humans. The primary aim of this study is to inhibit the overactivity of COX-2, a key enzyme implicated in colorectal cancer. This research investigates the natural inhibitory potential of 20 flavonoid compounds against the COX-2 enzyme (PDB ID: 5KIR). Molecular docking was performed to evaluate binding affinities and interaction patterns. Rofecoxib exhibited a binding affinity of ∆G = −7.6 kcal/mol against COX-2. Notably, several flavonoid-based natural compounds demonstrated even higher binding affinities: 4-Hydroxywogonin (∆G = −9.9 kcal/mol), 2’,3’,5,7-Tetrahydroxyflavone (∆G = −9.5 kcal/mol), and 2’R,4’-Hydroxyemoroidocarpan (∆G = −9.4 kcal/mol). These findings exhibit significant binding to COX-2, indicating their potential as anti-inflammatory agents. This research lays the groundwork for novel flavonoid-based therapeutics targeting COX-2-related pathways.