In Silico Evaluation of Curcumin Binding Affinity toward Key Inflammatory Targets: COX-2, TNF-α, and NF-κB

Abstract

Introduction — Inflammation is a biological response to tissue injury or infection involving key mediators such as cyclooxygenase-2 (COX-2), tumor necrosis factor-alpha (TNF-α), and nuclear factor kappa B (NF-κB). Curcumin, the major bioactive compound of Curcuma longa, has demonstrated potential anti-inflammatory properties. This study evaluated the anti-inflammatory potential of curcumin using an in silico approach.

Methods — Biological activity was predicted using PASS Online, drug-likeness was evaluated according to Lipinski's Rule of Five, molecular docking was performed with PyRx AutoDock Vina against COX-2, TNF-α, and NF-κB, and pharmacokinetic and toxicity profiles were predicted using ADMET analysis.

Results — Curcumin showed anti-inflammatory potential with a Probability of Activity (Pa) of 0.667 and a Probability of Inactivity (Pi) of 0.019. The compound satisfied all Lipinski's Rule of Five criteria without violations. Molecular docking produced binding affinities of −7.5, −5.8, and −6.1 kcal/mol against COX-2, TNF-α, and NF-κB, respectively, with ligand–protein interactions dominated by hydrogen bonds and hydrophobic interactions. ADMET prediction indicated high human intestinal absorption (82.19%), strong plasma protein binding (97.1%), and no predicted mutagenic or carcinogenic effects.

Conclusion — Curcumin exhibits favorable drug-like properties and promising multitarget anti-inflammatory activity, supporting its potential as a candidate for anti-inflammatory drug development. Further in vitro and in vivo studies are required to confirm these findings.