## 3 Results and Discussion
### Admt
\begin{table}
\begin{tabular}{c c c c c c} \hline \hline
**Pharmacokinetics** & **Mol1** & **Mol2** & **Mol3** & **Mol4** & **Mol5** \\ \hline \multicolumn{6}{c}{Absorption} \\ \hline Caco-2 cell 1 permeability (nm/s) \textgreater{} 20 & 3.93 & 19.77 & 6.45 & 19.23 & 19.67 \\ Human intestinal absorption & 86.03 & 79.45 & 26.88 & 84.73 & 40.14 \\ (HIA \%) 70 to 100\% & 55.97 & 0.154 & 51.38 & 27.24 & 4.20 \\ Water solubility (g/L) & \multicolumn{1}{c}{} & \multicolumn{1}{c}{} & \multicolumn{1}{c}{} & \multicolumn{1}{c}{} & \\ P-glycoprotein inhibition & \multicolumn{1}{c}{} & \multicolumn{1}{c}{} & \multicolumn{1}{c}{} & & \\ a substrate of it indicates high levels of absorption & \multicolumn{1}{c}{} & \multicolumn{1}{c}{} & & & \\ \hline \multicolumn{6}{c}{Distribution} \\ \hline Blood-brain barrier penetration & & & & & \\ (C.brain/C.blood) & 0.28 & 0.08 & 0.03 & 0.24 & 0.04 \\ \textgreater{}2 cross the blood-brain barrier easily & & & & & \\ MDCK 2 cell permeability (nm/s) & & & & & \\ Low (\textless{}1 nm/s), moderate (1–10 nm/s), and high & 0.55 & 0.46 & 0.57 & 0.57 & 0.49 \\ (\textgreater{}10 nm/s) & & & & & \\ Plasma protein binding (\%) & & & & & \\
80 to 100\% is considered high, 50 to 80\% & 49.01 & 60.14 & 32.43 & 38.70 & 56.46 \\ (moderate), \textless{}50\% (low) & & & & & \\ Skin permeability & & & & & \\ (logKp 3, cm/hour) & \(-5.19\) & \(-5.02\) & \(-5.12\) & \(-5.20\) & \(-4.82\) \\ \(\textless{}-2.5\) considered high permeable & & & & & \\ \hline \multicolumn{6}{c}{Metabolism} \\ \hline Cytochrome P450 2C19 inhibition & Non & Inhibitor & Non & Non & Inhibitor \\ Cytochrome P450 2C9 inhibition & Non & Non & Non & Non & Non \\ Cytochrome P450 2D6 inhibition & Inhibitor & Inhibitor & Inhibitor & Inhibitor & Inhibitor \\ Cytochrome P450 2D6 substrate & Substrate & Substrate & Substrate & Substrate & Substrate \\ Cytochrome P450 3A4 inhibition & Non & Inhibitor & Non & Non & Non \\ Cytochrome P450 3A4 substrate & Weakly & Weakly & Weakly & Weakly & Weakly \\ \hline \multicolumn{6}{c}{Toxicity} \\ \hline Ames test & Mutagen & Mutagen & non-mutagen & Mutagen & Mutagen \\ Carcinogenicity (Mouse) & Negative & Negative & Negative & Negative & Negative \\ Carcinogenicity (Rat) & Positive & Positive & Negative & Positive & Negative \\ HERG 4.inhibition & Medium risk & Medium risk & low\_risk & Medium risk & Ambiguous \\ TA100 (+S9) & Positive & Positive & Negative & Positive & Negative \\ TA100 (\(-\)S9) & Negative & Negative & Negative & Negative & Negative \\ Ames TA1535 (+S9) & Positive & Negative & Negative & Positive & Negative \\ Ames TA1535 (\(-\)S9) & Positive & Positive & Negative & Positive & Positive \\ \hline \hline \end{tabular}  
* Human colorectal carcinoma, 2 Mandin Darby Canine Kidney, 3 skin permeability constant, 4 Human ether-related gene channel.  
\end{table} 
Table 4: The ADMT properties of the five studied compounds. xenobiotics are rapidly metabolized, they may not remain in the bloodstream for a sufficient duration to exert their desired effects. Conversely, if they are metabolized slowly, they may accumulate and lead to toxicity, although they may also demonstrate effectiveness. The toxicity profile of the compounds indicates consistent outcomes in terms of mutagenicity in the Ames tests (as shown in Table 4). The majority of the compounds exhibited negative results for mouse carcinogenicity, however, most of them were positive for rat carcinogenicity, which is more closely related to human genes, indicating a high potential for carcinogenicity, particularly with high doses and prolonged exposure. The inhibition of human ether-related gene channels posed a moderate risk, except for Mol3. Consequently, it is crucial to adjust drug doses, administration routes, and treatment durations to address certain weak pharmacokinetic parameters.