Computational Comparison of the Binding Affinity of Selective and Nonselective NSAIDs to COX-2 Using Molecular Docking
Authors
-
Doménica Flores
Universidad de Cuenca/ Departamento de Química Aplicada/ Cuenca/ Ecuador
https://orcid.org/0009-0007-6894-5405
- Carola Jerves Universidad de Cuenca/ Departamento de Química Aplicada/ Cuenca/ Ecuador
DOI:
https://doi.org/10.70099/BJ/2025.02.02.3Keywords:
NSAIDs, active site, COX-2, Docking, selectivityAbstract
Cyclooxygenase-2 (COX-2) plays a key role in inflammation, making it a prime target for nonsteroidal anti-inflammatory drugs (NSAIDs). This study uses molecular docking to compare the binding affinities of four nonselective NSAIDs (aspirin, ibuprofen, diclofenac, naproxen) and three selective COX-2 inhibitors (celecoxib, rofecoxib, etoricoxib) to COX-2. Simulations with AutoDock4 and AutoDock Vina revealed distinct differences in binding profiles and selectivity. Selective COX-2 inhibitors exhibited stronger binding affinities, with etoricoxib achieving -11.22 kcal/mol (AutoDock4), driven by key hydrogen bonds and π interactions. Nonselective NSAIDs, such as diclofenac (-8.08 kcal/mol), showed moderate affinity but lacked specificity, targeting both COX isoforms and increasing gastrointestinal side effects. AutoDock4 provided detailed conformational analysis, while AutoDock Vina complemented with faster but less detailed results. This research highlights the structural interactions underlying NSAID efficacy and side effects, offering valuable insights for drug design. Selective inhibitors provide improved safety profiles for long-term use, while nonselective NSAIDs remain effective for short-term treatments. These findings emphasize the importance of computational tools in optimizing NSAID selectivity and efficacy, paving the way for developing safer anti-inflammatory therapies.
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