In-silico molecular docking of ezetimibe and malic acid into cyclooxygenase enzymes

Nureen Farihah Mohd Soufi

Authors

Nureen Farihah Mohd Soufi Faculty of Pharmacy, University Sultan Zainal Abidin, Terengganu, Malaysia

Keywords:

Molecular docking, In-silico, Cyclooxygenase enzymes, COX-1, COX-2, Ezetimibe, Malic Acid, Ibuprofen, Celecoxib, Anti-inflammatory

Abstract

The study of interactions of malic acid and ezetimibe molecules with cyclooxygenase enzymes is facilitated by molecular docking, which provides information on probable binding modalities and affinities important in drug discovery and studying molecular mechanisms. Ezetimibe, with lipid-lowering action, and malic acid, with antioxidant and gastroprotective action, have shown individual therapeutic efficacy. However, their combined action on COX enzymes is poorly studied.

Ligand and enzyme structures were obtained from PubChem and the Protein Data Bank (PDB). Molecular Operating Environment (MOE) 2015.10 was used for ligand preparation, protein optimisation, and docking. Biovia Discovery Studio 4.5 was used for 2D and 3D representation of protein-ligand interactions. Binding energy, RMSD values, hydrogen bonding, and hydrophobic interaction parameters were compared to establish affinity and stability.

Ezetimibe displayed potent binding affinity against both COX-1 (−8.364 kcal/mol) and COX-2 (−8.7288 kcal/mol), whereas malic acid showed weak interactions (−4.63 kcal/mol). The combination enhanced COX-2 affinity (−8.8037 kcal/mol) with a slight decrease in COX-1 affinity (−7.7017 kcal/mol), indicating increased COX-2 selectivity.The ezetimibe–malic acid combination exhibited the greatest COX-2 binding among individual ligands and reference NSAIDs with lower COX-1 affinity, indicating a diminished risk for gastrointestinal side effects. The results endorse the prospects of this combination as a dual-action therapeutic with anti-inflammatory and lipid-lowering properties.

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