In silico anti-inflammatory activities of abelmoschus esculentus derived ligands on COX-2

This study investigated the inhibitory potential of selected polyphenolic compounds identified in Abelmoschus esculentus (okra) against human Cyclooxygenase-II (COX-2), an enzyme implicated in inflammation, using molecular docking and in silico toxicity analysis. The compounds—ferulic acid, caffeic acid, and vanillic acid—were screened and docked using PyRx 0.8, with ibuprofen and Vioxx serving as reference inhibitors. The 3D crystal structure of COX-2 bound to Vioxx (PDB ID: 1PXX) was retrieved and prepared for docking. Ferulic acid demonstrated a binding energy of –5.1 kcal/mol, forming hydrogen bonds with ARG311, THR561, LYS2253, and LEU2246. Caffeic acid displayed a slightly better binding energy of –5.2 kcal/mol and interacted with ARG311, ASN570, and ASP2268. Vanillic acid, with a binding energy of –4.7 kcal/mol, formed bonds with ASN570, ILE558, ARG311, and LYS557. Comparatively, ibuprofen and Vioxx recorded binding energies of –5.5 kcal/mol and –6.0 kcal/mol, respectively, affirming their higher affinity to COX-2. RMSD values for all docked compounds were 0.00 Å, confirming good binding pose stability. In silico toxicity analysis using the ProTox-II platform revealed LD₅₀ values of 1772 mg/kg, 2980 mg/kg, and 2000 mg/kg for ferulic acid, caffeic acid, and vanillic acid, respectively. Ferulic acid and vanillic acid were classified as non-toxic (Class 4) and inactive for carcinogenicity, while caffeic acid, although classified as Class 5, showed predicted carcinogenic potential. Drug-likeness profiling using SwissADME confirmed that all test compounds satisfied Lipinski’s and Ghose’s rules, indicating favorable oral bioavailability. The findings suggest that ferulic and vanillic acids possess promising anti-inflammatory potential as natural COX-2 inhibitors with acceptable safety profiles. These compounds may serve as candidates for further development into plant-based therapeutics, subject to experimental validation and pharmacokinetic assessment.