## 3 Results and Discussion
### Cheminformatics Prediction
#### 3.2.2 Molecular Docking  
Docking of the Compounds **(5-7)** _anti_**, **(5-7)** _syn_**, and Marotiline **9** into **4 xnx** Model  
The binding affinity of the compounds has been investigated and recorded as MolDock score (Table 5, Figure S8). The compound **7** _syn_** has the highest MolDock score, \(-\)117.691, while compound **5** _syn_** has the lowest MolDock, \(-\)89.0117, Table 5. In contrast to marotiline, the compounds **5** _anti_**, **5** _syn_**, **6** _syn_**, **7** _anti_**, and **7** _syn_** exhibit no hydrogen bond. Their binding with protein model is due to their steric interaction with the amino acids; Phe 325, Val 327, Asp 121, Val 120, Phe 43, Gly 425, Tyr 123, and Tyr 124. The compound **6** _anti_** exhibits hydrogen bond with distance 3.09982 A between its oxygen and nitrogen of Tyr 124, and marotiline **9** exhibits hydrogen bond with distance 2.92323 A between its nitrogen and amine oxygen of Ser 421, Figure 1. \begin{table}
\begin{tabular}{c c c} \hline \hline \multirow{2}{*}{**Compound**} & \multicolumn{2}{c}{**Activity/Pa**} \\ \cline{2-3}  & _Antidepressant_ & _Phobic Disorders Treatment_ \\ \hline
**5** _anti_** & 0.226 & 0.877 \\
**5** _syn_** & 0.226 & 0.877 \\
**6** _anti_** & 0.142 & 0.875 \\
**6** _syn_** & 0.142 & 0.875 \\
**7** _anti_** & 0.169 & 0.842 \\
**7** _syn_** & 0.169 & 0.842 \\
**Maprotiline 9** & 0.626 & 0.897 \\ \hline \hline \end{tabular}
\end{table} 
Table 4: Prediction of antidepressant and anti-phobic activities of the compounds **(5–7)** _anti_**, **(5–7)** _syn_**, and marotiline **9**. \begin{table}
\begin{tabular}{c c c c c c c c c} \hline \hline  & \multicolumn{3}{c}{**dark Model**} & \multicolumn{3}{c}{**2 QIU Model**} & \multicolumn{3}{c}{**3 GWU Model**} \\ \hline
**Compound** & **H-Bond (Length A)** & **Steric Interaction** & **MulDock Score** & **H-Bond (Length A)** & **Steric Interaction** & **MulDock Score** & **H-Bond (Length A)** & **Steric Interaction** & **MulDock Score** \\ \hline \multirow{4}{*}{**5 anti**} & \multirow{4}{*}{-} & \multicolumn{3}{c}{Phe 325, Val 327,} & \multicolumn{3}{c}{He 111, Tyr 108,} & \multirow{4}{*}{Cin 34, (2.7924)} & \multirow{4}{*}{Cin 34, (2.7924)} & \multirow{4}{*}{Cin 34, (2.7924)} & \multirow{4}{*}{Cin 34, (2.7924)} & \multirow{4}{*}{Cin 34, (2.7924)} \\  & & \multicolumn{3}{c}{Age 121, Val 120,} & \multicolumn{3}{c}{-95.1967} & \multicolumn{3}{c}{-} & \multicolumn{3}{c}{Age 30, 100, 25,} \\  & & \multicolumn{3}{c}{Phe 43, Gly 425} & \multicolumn{3}{c}{} & \multicolumn{3}{c}{} & \multicolumn{3}{c}{} \\  & & & & & & & & \\  & & & & & & & & \\  & & & & & & & & \\
5 sym & - & & Tyr 123, Tyr 124 & \(-\)89.0117 & - & [PERSON] 29, Phe 253, & \(-\)81.0802 & - & [PERSON] 29, Phe 253, (Ch 34, -\)  
Docking of the Compounds **(5-7) _anti_**, (5-7) _syn_, and Maprotiline **9** into **2 QJU** Model  
The compound **7 _anti_** has the highest MolDock score, \(-103.8\), with hydrogen bond interaction (2.74666 A) between its oxygen and the amine of Arg 30, while **5 _syn_** has the lowest MolDock score, \(-81.0802\), with no hydrogen bonding, Table 5. The amino acids Phe 320 and Arg 30 may play a significant role in the binding affinity, since they participate in the steric interactions of all docked compounds. Furthermore, Arg 30 participates in the hydrogen bonding with the two docked compounds; **6 _anti_** and **7 _syn_**. Maprotiline exhibits hydrogen bond with distance 2.75112 A between its nitrogen and oxygen of Asp 404, Figure 2. The other amino acids that affect the binding of the compounds are listed in Table 5.  
Docking of the Compounds **(5-7) _anti_**, (5-7) _syn_**, and Maprotiline **9** into **3 GWU** Model  
Although compound **7 _syn_** has the highest MolDock score, \(-104.221\), it has no hydrogen bond, while **5 _anti_** has the lowest MolDock score, \(-79.4448\), with hydrogen bond (2.79245 A), Figure 3. The other docked compounds have no hydrogen bonding, so the hydrogen bonding is not more significant for enhancing binding affinity, (Table 5, Figure S9).