Potential Cyclooxygenase (COX-2) Enzyme Inhibitors from Myrica nagi-from in-silico to in-vitro Investigation

Objectives: Our principal focus was to identify COX‑2 enzyme inhibitors, safer and natural anti‑inflammatory compounds from M. nagi. Protein–ligand interaction has a significant role in structure‑based drug design. Materials and Methods: Sixty‑eight phytochemicals were therefore screened and evaluated for their binding energies with COX‑2. These phytoconstituents were screened and analyzed for drug Likeliness along with Lipinski’s rule of five. The X‑ray crystallographic structure of the target COX‑2 (protein data bank [PDB] ID: 4PH9), obtained from PDB, was docked with PubChem structures of phytochemicals using AutoDock 4.2 that uses Lamarckian genetic algorithm. Further, myricetin was subjected to in vitro anti‑inflammatory assay using RAW‑264.7 cell lines and inhibitory concentration (IC50) value was also determined. Results: The myricetin, myricitrin, and corchoionoside‑C inhibited COX‑2 with − 6.52, −4.94, and − 4.94 Kcal/mol binding energies, respectively, comparable to ibuprofen. Eventually, bioactivity score and absorption distribution metabolism excretion‑toxicity properties showed considerable biological activities as G protein‑coupled receptor, nuclear receptor, protease inhibitor, and enzyme inhibitors for myricetin, myricitrin, and corchoionoside‑C phytochemicals. Molecular docking revealed hydrophobic interactions followed by four, nine, and four numbers of hydrogen bonds between myricetin, myricitrin, and corchoionoside‑C, respectively, within the binding site of COX‑2. Flavonol myricetin showed 112 µg/mL as IC50 value when it was subjected to in vitro cytotoxicity assay. These results clearly demonstrated that myricetin, myricitrin, and corchoionoside‑C could act as highly potential COX‑2 inhibitors. Therefore, in silico and in vitro studies revealed that of three best phytochemicals, myricetin could be promising candidate.