## 3 Results  
### COX-1 Interactions  
The interaction parameters of the selected terpen with COX-1, compared to arachidonic acid (AA), are summarized in Table 1.  
One of the fundamental parameters for evaluating ligand-enzyme interactions is the binding energy, expressed in kcal/mol. Lower binding energy values correlate with the formation of more stable ligand-enzyme complexes, which, in turn, indicate higher binding affinity. In the present study, AA exhibits the lowest binding energy (\(-\)7.53 kcal/mol), reflecting its strong interaction with COX-1. Among the analyzed terpen, menthol has the lowest binding energy (\(-\)6.56 kcal/mol), followed by camphor (\(-\)6.32 kcal/mol) and \(\beta\)-pinene (\(-\)6.31 kcal/mol), suggesting that these compounds possess relatively high affinity for COX-1. The inhibition constant (Ki) represents another indicator of the potential inhibitory activity of the studied molecules, with lower Ki values corresponding to greater inhibitory potential. The lowest Ki value is observed for AA (3.02 uM), consistent with its role as the natural substrate of COX-1. Among the terpen, menthol (15.50 uM) and camphor (23.37 uM) exhibit the lowest Ki values, suggesting that these compounds may exert inhibitory activity toward the enzyme. The root-mean-square deviation (RMSD) values, relative to the reference structure, provide insights into the extent of conformational changes undergone by the ligands upon binding. High RMSD values (>50 A) are recorded for all analyzed molecules, indicating significant spatial reorientation. The highest RMSD values are observed for camphor (67.64 A) and \(\beta\)-pinene (67.775 A), suggesting that these molecules undergo substantial conformational changes upon binding to COX-1. The total internal energy and torsional free energy provide additional insight into the molecular stability of the ligands. The highest torsional energy values are recorded forlinal (+1.49 kcal/mol) and AA (+4.47 kcal/mol), suggesting increased flexibility and a greater tendency for conformational changes. In contrast, menthol exhibits the lowest torsional energy (+0.60 kcal/mol), indicating a relatively stable conformation upon binding to COX-1. Unbound energy is a parameter reflecting the energetic state of the molecule in its free form. The lowest unbound energy is observed for AA (\(-\)1.61 kcal/mol), consistent with its high binding affinity. \begin{table}
\begin{tabular}{l c c c c c c c} \hline
**COX-1** & **Limonene** & **Camphor** & **Linalool** & **Menthol** & **\(\alpha\)-Pinene** & **\(\beta\)-Pinene** & **AA** \\ \hline Conformations & 2 & 13 & 33 & 20 & 54 & 60 & 9 \\ \hline RMSD from & & & & & & & \\ Reference & 59.121 A & 67.643 A & 66.924 A & 67.481 A & 66.995 A & 67.775 A & 57.255 A \\ Structure & & & & & & & \\ \hline Binding Energy & \(-\)5.99 & \(-\)6.32 & \(-\)5.82 & \(-\)6.56 & \(-\)6.20 & \(-\)6.31 & \(-\)7.53 \\  & kcal/mol & kcal/mol & kcal/mol & kcal/mol & kcal/mol & kcal/mol & kcal/mol \\ \hline Inhibition & & 40.60 μM & 23.37 μM & 54.64 μM & 15.50 μM & 28.74 μM & 23.61 μM & 3.02 μM \\ Constant, Ki & & & & & & & \\ \hline Total Internal & \(-\)0.13 & +0.00 & \(-\)0.33 & \(-\)0.17 & +0.00 & +0.00 & \(-\)1.61 \\ Energy & kcal/mol & kcal/mol & kcal/mol & kcal/mol & kcal/mol & kcal/mol & kcal/mol \\ \hline Torsional Free & +0.30 & +0.00 & +1.49 & +0.60 & +0.00 & +0.00 & +4.47 \\ Energy & kcal/mol & kcal/mol & kcal/mol & kcal/mol & kcal/mol & kcal/mol & kcal/mol \\ \hline Unbound Energy & \(-\)0.13 & +0.00 & \(-\)0.33 & \(-\)0.17 & +0.00 & +0.00 & \(-\)1.61 \\ kcal/mol & kcal/mol & kcal/mol & kcal/mol & kcal/mol & kcal/mol & kcal/mol \\ \hline \end{tabular}
\end{table} 
Table 1: In silico docking results for interactions between selected terpen and COX-1: binding energy, conformational parameters, inhibition constants (Ki), and energy descriptors compared to arachidonic acid (AA). In summary, AA exhibits the highest affinity for COX-1, consistent with its role as the enzyme's natural substrate.