## 4 Discussion
### Structure-Activity Relationship (SAR) Analysis of Terpenes  
The differential binding affinities and interaction profiles observed across the six terpenes and four enzymes highlight crucial structure-activity relationships, emphasizing how subtle structural variations dictate their inhibitory potential. Bicyclic Monoterpenes: Both pinenes are bicyclic monoterepenes with a rigid bicyclo [3.1.1]heptane core. The primary structural difference lies in the position of the double bond: \(\alpha\)-pinene possesses an endocyclic double bond, while \(\beta\)-pinene has an exocyclic one. This structural rigidity likely contributes to their consistent interaction patterns with COX-1 and COX-2, particularly with residues like TYR385, HIS388, and TRP387. The compact, rigid structure of pinenes allows for stable hydrophobic interactions within the relatively narrow channels leading to the active sites of these cyclooxygenaseases. Their less favorable binding to 5-LOX and PLA\({}_{2}\), compared to some other terpen, suggests that their bicyclic framework might not optimally fit the active site geometries or hydrophobicity profiles of these latter enzymes, with the notable exception of \(\beta\)-pinene's direct interaction with PLA\({}_{2}\) catalytic residues (PHE5, CY544, HIS47). This specific interaction of \(\beta\)-pinene might be facilitated by the slightly altered spatial presentation of its exocyclic double bond, allowing for precise contacts. Cyclic Monoterpene Alcohols/Ketones: Menthol (a cyclic alcohol) and camphor (a bicyclic ketone) both contain a six-membered ring (cyclohexane in menthol, part of a bicyclic system in camphor) and oxygen-containing functional groups (-OH in menthol, C=O in camphor). Menthol (5-Methyl-2-(propan-2-yl)cyclohexan-1-ol) is a cyclic monoterepene alcohol. Its hydroxyl group can participate in hydrogen bonding, while its bulky isopropyl and methyl groups contribute to hydrophobic interactions. Its consistently low binding energies and Ki values across all four enzymes, especially for COX-1, 5-LOX, and PLA\({}_{2}\), indicate its versatile binding capabilities. The presence of the hydroxyl group provides an anchor point for polar interactions, while its overall compact, non-planar structure allows it to snugly fit into various binding pockets. Camphor (1,7,7-trimethylbicyclo[2.2.1]heptan-2-one) is a bicyclic monoterepene ketone. The ketone group provides a site for hydrogen bonding (as an acceptor), and its rigid, compact structure with three methyl groups contributes significantly to hydrophobic interactions. Its favorable binding to COX-1 and COX-2 is likely due to its shape complementarity with the relatively confined active sites of these enzymes, similar to the pinenes, but with the added polar interaction from the carbonyl oxygen. The rigid bicyclic structure might limit its conformational adaptability for optimal binding to 5-LOX and PLA\({}_{2}\) compared to more flexible terpen. Monocyclic Monoterpene: Limonene (1-Methyl-4-(prop-1-en-2-yl)cyclohex-1-ene) is a cyclic monoterpene characterized by a cyclohexene ring with two double bonds (one endocyclic and one exocyclic isopropenyl group). Its relative flexibility compared to the bicyclic pinches, combined with its hydrophobic nature, appears to be highly advantageous for interactions with 5-LOX and PLA\({}_{2}\). Its exceptional binding affinity to 5-LOX and PLA\({}_{2}\), even surpassing AA in Ki for PLA\({}_{2}\), suggests that its structure allows for an optimal fit into the active sites of these enzymes. The presence of two double bonds provides potential sites for \(\pi\)-stacking or hydrophobic interactions within the binding pocket. Acyclic Monoterpene Alcohol: Linalool (3,7-dimethyl-1,6-octadien-3-ol) is an acyclic monoterpene alcohol, making it the most conformationally flexible among the investigated terpen. Its acyclic nature allows for a wide range of conformations, as evidenced by its higher torsional free energy.