## 3 Results and Discussion
### Cheminformatics Prediction
#### 3.2.4. ADMET Prediction
The compounds **5 _anti_**, **5 _syn_**, **6 _anti_**, **6 _syn_**, and reference drug **9** are considered neither substrates nor inhibitors for the P450 CYP119 enzyme, while the **7 _anti_** and **7 _syn_** could behave either as substrates or inhibitors. The compounds **(5-7) _anti_** and **(5-7) _syn_** have a moderate half-life (T\({}_{1/2}\)) time and low clearance rate (CL). The **5 _anti_** and its isomer **5 _syn_** have higher T\({}_{1/2}\) and CL, but reference drug **9** has the highest (T\({}_{1/2}\): 2.174, 2.34, and 3.401 h; CL: 1.424, 1.425, and 2.599 mL/min/kg, respectively). \begin{table}
\begin{tabular}{c c c c c c c c c c c c c c c} \hline \hline \multirow{2}{*}{**Compound**} & \multicolumn{2}{c}{**MW**} & \multirow{2}{*}{**HBA**} & \multirow{2}{*}{**HBD**} & \multicolumn{2}{c}{**TTSA**} & \multicolumn{2}{c}{**Consensus**} & \multirow{2}{*}{**MR**} & \multicolumn{2}{c}{**GI**} & \multicolumn{2}{c}{**BBB**} & \multicolumn{2}{c}{**P-gp**} & \multirow{2}{*}{**Lipinski**} & \multicolumn{2}{c}{**Bioavailability**} & \multicolumn{2}{c}{**PAINS**} & \multicolumn{2}{c}{**Brenk**} \\  & **(g/mol)** & & & **(A\({}^{\circ}\))** & & **Log Po/w \({}^{\circ}\)** & & & **Absorption** & & **Permanet** & **Substrate** & & **Score** & **(alert)** & **(alert)** \\ \hline
**5 _anti_** & 300.18 & 1 & 0 & 23.79 & 4.43 & 80.98 & High & Yes & Yes & Yes **\({}^{**}\)** & 0.55 & 0 & 0 \\
**5 _synt_** & 300.18 & 1 & 0 & 23.79 & 4.42 & 80.98 & High & Yes & Yes & Yes **\({}^{**}\)** & 0.55 & 0 & 0 \\
**6 _anti_** & 358.22 & 3 & 0 & 50.09 & 4.25 & 91.92 & High & Yes & Yes & Yes & 0.55 & 0 & 0 \\
**6 _synt_** & 358.22 & 3 & 0 & 50.09 & 4.22 & 91.92 & High & Yes & Yes & Yes & 0.55 & 0 & 0 \\
**7 _anti_** & 415.33 & 2 & 0 & 42.52 & 5.40 & 109.04 & Low & No & No & Yes **\({}^{**}\)** & 0.55 & 0 & 0 \\
**7 _synt_** & 415.33 & 2 & 0 & 42.52 & 5.38 & 109.04 & Low & No & No & Yes **\({}^{**}\)** & 0.55 & 0 & 0 \\
**Maprotiline 9** & 277.40 & 1 & 1 & 12.03 & 4.30 & 88.32 & High & Yes & Yes & Yes **\({}^{**}\)** & 0.55 & 0 & 0 \\ \hline \hline \multicolumn{11}{c}{MW: Molecular Weight: HBA: Num. H-Bond Concorts: HBD. Num. H-Bond Concorts: HBD. Num. H-Bond Concorts: HTCap: Topological Polar Surface Area: P-M-Poor-Moderate; P: Poor; GL: GastrointestinalJ; BBB Blood-Brain Barrier; P-gg; P-g; P-Gyrupcuit; \({}^{**}\)Average of five prediction, \({}^{**}\)1 violation: MQCOF \(\times\) 415, PAINS: Pan-assay Interference Compounds.} \\ \hline \hline \end{tabular}
\end{table} 
Table 6: Physicochemical, pharmacokinetics, and medicinal chemistry properties of the compounds **(5–7) _anti_, **(5–7) _synt_**, and Mportiline 9 using SwissADME server. \begin{table}
\begin{tabular}{c c c c c c c c c c c c c c} \hline \hline \multirow{2}{*}{**Compound**} & \multicolumn{2}{c}{**Absorption**} & \multicolumn{2}{c}{**Distribution**} & \multicolumn{2}{c}{**Metabolism; P80 CYP**} & \multicolumn{2}{c}{**Elimination**} \\ \cline{2-13}  & \multicolumn{2}{c}{**Caco-2**} & \multicolumn{2}{c}{**P (cm/s)**} & \multicolumn{2}{c}{**Pgp (I)**} & \multicolumn{2}{c}{**Pgp (S)**} & \multicolumn{2}{c}{**HIA**} & \multicolumn{2}{c}{**PP8\%**} & \multicolumn{2}{c}{**VD**} & \multicolumn{2}{c}{**1A2**} & \multicolumn{2}{c}{**74**} & \multicolumn{2}{c}{**119**} & \multicolumn{2}{c}{**T\({}_{\text{1}}\)**} & \multicolumn{2}{c}{**H**} \\  
Drug toxicology is one of the essential areas in the preclinical investigation, since the toxicity is a major factor leading for drug attrition at discovery and development phases [67]. Thus the in silico reliable prediction of compound toxicity is important in order to reduce expenses and to save a lot of time during the drug discovery and development [68]. The toxicity risk of the compounds **(5-7) _anti_** and **(5-7) _syn_**, and maprotiline **9**, was assessed quantitatively by ADMETlab server.