## 3 Results
### Blind Docking Results
These diagrams illustrate the spatial arrangement and nature of non-covalent contacts, including conventional hydrogen bonds (green), \(\pi\)-\(\sigma\) interactions (purple), and hydrophobic contacts such as alkyl or \(\pi\)-alkyl interactions (pink). Notably, menthol and camphor form hydrogen bonds with TYR385 and HIS388, residues known to be essential for COX-1 catalytic activity. In contrast, \(\alpha\)-pinene and \(\beta\)-pinene primarily establish hydrophobic interactions within the binding cavity. These 2D diagrams complement the numerical docking data and offer a structural rationale for the observed differences in binding energy and inhibition constants among the studied terpen. Figure 5: The 2D visualization of ligand–enzyme interactions between the selected terpen and the COX-1 active site. Interaction diagrams of the six investigated terpenes—(**a**) limonene, (**b**) camphor, (**c**) linalool, (**d**) menthol, (**e**) \(\alpha\)-pinene, and (**f**) \(\beta\)-pinene—and the reference ligand arachidonic acid (**g**) with the active site of COX-1. The diagrams depict the key non-covalent interactions, including conventional hydrogen bonds (green), \(\pi\)–sigma–(purple), and alkyl or \(\pi\)–alkyl hydrophobic contacts (pink). Amino acid residues involved in the interaction are labeled and positioned according to their spatial orientation within the active site. COX-2 is inducible under inflammatory conditions and is a preferred target for selective inhibitors. The primary amino acid residues involved in terpene interactions include TYR385, HIS388, TRP387, PHE381, and VAL349. Limonene again shows affinity for PHE381. In the case of camphor, no overlap can be observed between the ligand-enzyme interaction residues and the active site residues of COX-2. Linalool, menthol, \(\alpha\)-pinene, and \(\beta\)-pinene demonstrate stable binding with HIS388 and TYR385, consistent with the patterns observed for COX-1. \(\alpha\)-Pinene and \(\beta\)-pinene also exhibit specific affinity for TRP387, which may influence their selectivity toward COX-2. To complement the numerical docking data, 2D interaction diagrams are generated to depict the binding modes of the investigated terpen within the COX-2 active site (Figure 6). These visualizations provide structural support for the observed affinity trends and help rationalize the inhibitory potential of each terpene based on its interaction fingerprint within the COX-2 enzyme. Figure 6: The 2D visualization of ligand–enzyme interactions between the selected terpen and the COX-2 active site. Interaction diagrams of the six investigated terpenes—(**a**) limonene, (**b**) camphor, (**c**) linalool, (**d**) menthol, (**e**) \(\alpha\)-pinene, and (**f**) \(\beta\)-pinene—and the reference ligand arachidonic acid (**g**) with the active site of COX-2. The diagrams depict the key non-covalent interactions, including conventional hydrogen bonds (green), \(\pi\)–sigma–Sigma (purple), and alkyl or \(\pi\)–alkyl hydrophobic contacts (pink). Amino acid residues involved in the interaction are labeled and positioned according to their spatial orientation within the active site. 5-LOX catalyzes the first step in leukotriene biosynthesis, which plays a critical role in chronic inflammatory diseases. The key amino acid residues involved in ligand binding include HIS367, HIS372, HIS550, YYR181, and TRP599. Among the tested compounds, only linalool shows stable contacts with LEU414, TRP599, ALA603 and YYR181, which overlap with its interaction profile with COX-2. For the remaining terpen, no overlap is observed between the ligand-enzyme interaction residues and the amino acid sequence of the 5-LOX active site. In addition to binding affinity data, the predicted interactions of the terpen with 5-LOX are visualized using 2D ligand-enzyme diagrams (Figure 7). PLA\({}_{2}\) is responsible for releasing AA from membrane phospholipids, representing the initial step in the inflammatory cascade. The main contact residues in the enzyme's active site include HIS47, CYS44, YYR51, and PHE5.