## 3 Results and Discussion
### In Silico Study  
#### 3.3.1 Assessment of ADMET Properties and Drug Likeness of the Screened Molecules  
Modern research aimed at searching for new medicinal substances uses many computational methods that enable preliminary prediction of properties essential for assessing the probability that a chemical compound may become a drug [63]. As part of our work, for the tested compounds, pharmacokinetics and toxicity were assessed using in silico methods. Calculations of ADMET parameters for the tested compounds were performed using the pKCSM (2015) software and are presented in Table 6.  
In order to initially assess the ease of absorption of a substance, various parameters should be considered. Both human intestinal absorption (HIA), human intestinal permeability (Caco-2), and the ability to interact with P-glycoprotein, the biological barrier responsible for the excretion of toxins and xenobiotics (PgP parameter), determine potential drug absorption difficulties. The HIA values obtained for the tested compounds **1**, 3-9, defining the percentage of the substance that will be absorbed by the human intestine, range from 52.222 to 100.000 and indicate good absorption (a value less than 30% indicates poor absorption). The highest Caco-2 permeability expi \begin{table}
\begin{tabular}{c c c c c c c c c c c} \hline \hline \multirow{2}{*}{**Parameter**} & \multicolumn{8}{c}{**Compound**} \\ \cline{2-11}  & **1** & **3** & **4** & **5** & **6** & **7a** & **7b** & **8a** & **8b** & **9** \\ \hline Water solubility & \(-5.492\) & \(-5.343\) & \(-5.504\) & \(-3.366\) & \(-3.325\) & \(-2.921\) & \(-2.918\) & \(-2.919\) & \(-2.915\) & \(-3.04\) \\ \hline Caco-2 permeability & 1.321 & 0.742 & 0.66 & 0.464 & 0.498 & 0.228 & 0.243 & 0.261 & 0.277 & 0.547 \\ \hline HIA & 100 & 97.799 & 94.528 & 83.47 & 96.189 & 52.222 & 58.517 & 64.94 & 71.235 & 70.09 \\ \hline pgP-substrate & no & yes & no & no & no & no & no & no & no \\ \hline pgP-I-inh. & yes & yes & no & no & no & no & no & no & no \\ \hline pgP-II-inh. & yes & yes & yes & yes & yes & yes & yes & yes & yes & yes \\ \hline BBB permeability & \(-0.467\) & \(-0.105\) & \(-0.541\) & \(-0.71\) & \(-0.686\) & \(-1.351\) & \(-1.373\) & \(-1.327\) & \(-1.348\) & \(-0.083\) & **D** \\ \hline CYP2D6 substr. & no & no & no & no & no & no & no & no & no & no \\ \hline CYP3A4 substr. & yes & yes & yes & yes & yes & yes & yes & yes & yes & yes \\ \hline CYP1A2 inh. & no & no & no & no & no & no & no & no & no \\ \hline CYP2C19 inh. & no & no & no & no & no & no & no & no & no \\ \hline CYP2C9 inh. & no & no & no & no & no & no & no & no & no \\ \hline CYP2D6 inh. & no & no & no & no & no & no & no & no & no \\ \hline CYP3A4 inh. & no & no & no & no & no & no & no & no & no \\ \hline Total clearance & 0.236 & \(-0.466\) & \(-0.259\) & \(-0.199\) & \(-0.410\) & \(-0.226\) & \(-0.344\) & \(-0.437\) & \(-0.556\) & \(-0.272\) & **E** \\ \hline AMES & no & no & no & no & no & no & no & no & no & no \\ \hline hERG I & no & no & no & no & no & no & no & no & no & no \\ \hline hERG II & no & no & no & no & no & no & no & no & no & no \\ \hline Max tolerated dose & & & & & & & & & & \\ (human) & \(-0.433\) & \(-0.095\) & 0.113 & 0.55 & 0.489 & 0.533 & 0.494 & 0.517 & 0.483 & 0.32 \\ Log mg/kg/day & & & & & & & & & & \\ \hline Oral rat acute LD\({}_{50}\) & 3.267 & 3.155 & 3.039 & 2.471 & 2.485 & 2.348 & 2.366 & 2.348 & 2.366 & 2.791 \\ \hline Hepatotoxicity & yes & no & no & no & no & no & no & no & no \\ \hline \hline \end{tabular}
\end{table} 
Table 6: Selected ADMET parameters of the tested compounds (pkCSM). culated for compounds **1** and **3**. They indicate high and good permeability (respectively, the values equal 1.321 for betulin **1** and 0.742 for compound **3**). According to the pkCSM prediction model, high Caco-2 permeability can be expected with a predicted value > 0.90. The logPapp value for the remaining compounds is in the range 0.228-0.660, which defines moderate Caco-2 permeability [45].