J Biomol Struct Dyn. 2026 Apr 10:1-13. doi: 10.1080/07391102.2026.2655804. Online ahead of print.
ABSTRACT
Cyclooxygenase-2 (COX-2) is a key therapeutic target for inflammatory diseases, cancer, and osteoarthritis (OA). Thus, several COX-2 inhibitors have been developed. However, their clinical use has been limited due to the cardiovascular, hepatic, and renal adverse effects. Given these limitations, the safer and more nuanced COX-2 inhibitors are needed. Curcumin (CU) from Curcuma longa, γ-oryzanol (GO) from rice bran oil, and sesamin (SM) (from sesame seed) were experimentally found to show the COX-2 inhibitory effect where a molecular detail is limited. Therefore, in this study, we investigated the binding mechanisms of CU, GO, and SM to COX-2 using Molecular Dynamics (MD) simulations. Our results show that all three ligands bind stably to COX-2 and adopt an I-shaped conformation spanning both the central binding site and proximal binding site. One end of each ligand, containing aromatic moiety, interacts with aromatic residues adjacent to heme group (Y385 for GO and W387 for CU and SM), while the remaining structure extends toward the proximal site. Hydrophobic interactions are the primary contributors to ligand binding, with CU and GO exhibiting stronger binding affinities than SM. Further experiments are needed. Collectively, these findings provide molecular-level insights that can support the rational development of plant-derived compounds as complementary or alternative therapeutics targeting inflammatory and pain-related disorders.
PMID:41960839 | DOI:10.1080/07391102.2026.2655804