In Silico Evaluation of Terpene Interactions with Inflammatory Enzymes: A Blind Docking Study Targeting Arachidonic Acid Metabolism

Terpenes are a structurally diverse group of plant-derived compounds increasingly recognized for their potential anti-inflammatory properties. In this study, blind molecular docking was performed to assess the interactions of six naturally occurring terpenes—α-pinene, β-pinene, menthol, camphor, limonene, and linalool—with four enzymes central to arachidonic acid (AA) metabolism: cyclooxygenase-1 (COX-1), cyclooxygenase-2 (COX-2), 5-lipoxygenase (5-LOX), and phospholipase A2 (PLA2). Arachidonic acid served as a reference ligand. Docking simulations using AutoDock 4.2 and the Lamarckian Genetic Algorithm enabled the evaluation of binding affinities, inhibition constants (Ki), and contact residues. Menthol and limonene showed strong binding affinity for 5-LOX, while α-pinene, menthol, and limonene exhibited higher affinity for PLA2 compared to AA. Residue-level interaction analysis revealed that β-pinene matched catalytic residues in PLA2, and all terpenes except camphor formed interactions with catalytically relevant residues in COX-2. All six compounds interacted with the active site of COX-1, whereas only linalool exhibited such interactions in 5-LOX. These findings suggest that specific terpenes may modulate inflammatory processes through interference with key enzymatic targets. However, further studies incorporating flexible-body docking and molecular dynamics are recommended to better elucidate the dynamic nature of these interactions and their potential pharmacological relevance.