In-Silico Molecular Docking and ADMET Evaluation of Selected Phytochemicals Targeting Cyclooxygenase-2 (COX-2) for Identification of Novel Anti-Inflammatory Drug Candidates

Rathnayaka Mudiyanselage Isuru Gayashan Wijiesinghe

Abstract: Inflammation is a central pathological mechanism underlying numerous chronic diseases, including arthritis, cardiovascular disorders, neurodegenerative conditions, and cancer. Cyclooxygenase-2 (COX-2) catalyzes prostaglandin biosynthesis and plays a central role in inflammatory responses. And represents a validated pharmacological target. Although selective COX-2 inhibitors such as celecoxib are clinically effective, long-term use is associated with cardiovascular, renal, and gastrointestinal adverse effects, necessitating the identification of safer therapeutic alternatives. This study aimed to identify potential COX-2 inhibitors from selected phytochemicals using structure-based molecular docking combined with in-silico pharmacokinetic and toxicity profiling. The three-dimensional structure of human COX-2 was retrieved from the Protein Data Bank, while bioactive phytochemicals were obtained from PubChem. Ligand optimization and AutoDock Vina was used for ligand optimization and molecular docking. Protein?ligand interactions were analyzed with Discovery Studio Visualizer. Drug-likeness was assessed according to Lipinski?s Rule of Five, and ADMET parameters were predicted using SwissADME and pkCSM platforms. Docking analysis revealed multiple phytochemicals exhibiting strong binding affinities ranging from -8.1 to -10.3 kcal/mol, exceeding that of the reference drug celecoxib. Key hydrogen bonding and hydrophobic interactions were observed with critical catalytic residues including Arg120, Tyr355, and Ser530, indicating stable ligand?enzyme complexes. ADMET profiling demonstrated favorable oral bioavailability, acceptable metabolic stability, and low predicted toxicity for selected lead compounds. These findings indicate that certain phytochemicals may bind COX-2 with favorable affinity and may serve as lead candidates for anti-inflammatory drug development. This study highlights the effectiveness of computational screening in accelerating early-stage drug discovery while minimizing experimental cost and time. Further in-vitro and in-vivo investigations are recommended to validate therapeutic efficacy.

Keywords: COX-2, molecular docking, phytochemicals, ADMET, anti-inflammatory drug discovery

How to Cite?: Rathnayaka Mudiyanselage Isuru Gayashan Wijiesinghe, "In-Silico Molecular Docking and ADMET Evaluation of Selected Phytochemicals Targeting Cyclooxygenase-2 (COX-2) for Identification of Novel Anti-Inflammatory Drug Candidates", Volume 15 Issue 2, February 2026, International Journal of Science and Research (IJSR), Pages: 105-108, https://www.ijsr.net/getabstract.php?paperid=SR26201092819, DOI: https://dx.doi.org/10.21275/SR26201092819