## 3 Biotransformation of Viniferins
### Prediction of Some Parameters That Describe Drug-Likeness
#### 5.2.3. Predicted Pharmacokine Properties of Chosen Viniferins and Vniferin-Based Compounds
This improvement in efficiency was assigned to a precisely chosen number, length, and positions of alkyl chains within the structure of particular flavonoids [91]. In general, compounds with log \(P_{\text{eff}}<2.00\) were considered those with low permeability, and derivatives with log \(P_{\text{eff}}>2.50\) were highly permeable [67; 124]. The log \(P_{\text{eff}}\) values (Table S4), ranging from 0.002 (26) to 0.603 (29), also indicated the limited permeability for the (25)-(27) set because this biopharmaceutically important descriptor was related to the prediction of the extension of absorption of these compounds in all human intestinal parts [187]. The increase in \(MW\), \(MR\), \(V_{\text{vdW}}\), and flexibility contributed more or less negatively to log \(P_{\text{eff}}\) as described with a corresponding \(r\) value of \(-0.862\) (\(MW\) versus log \(P_{\text{eff}}\)), \(-0.893\) (\(MR\) versus log \(P_{\text{eff}}\)), \(-0.919\) (\(V_{\text{vdW}}\) versus log \(P_{\text{eff}}\)), and \(-0.480\) (flexibility versus log \(P_{\text{eff}}\)), respectively (Table S6). Following only 'isolated' \(tPSA\) values, all discussed molecules could not be characterized by poor intestinal absorption through a passive mechanism because their \(tPSAs<140.0\) A\({}^{2}\)[102]. In addition, the majority of them would not be able to passively target the CNS following the criteria published in [103; 104]. This suggestion was also supported by the results of the Enalos Cloud Platform applet [132] (Table S4). This prediction was confirmed with the calculations via SwissADME [66] based on the generated WLOGP [94] and \(tPSA\)[99] parameters. However, these conclusions might not be completely consistent with the real situation, as [PERSON] et al. [188] observed. The authors focused on the treatment of [PERSON]'s disease and found that the naturally occurring **trans-\(\varepsilon\)-vinifera (19)** molecule passed a given physiological barrier. On the other hand, high lipophilicity of synthetic halogenated compounds (25)-(27) predicted via CLOGP 4.0 [93] indicated their greater potential to passively enter the CNS [104]. * The impact on P-glycoprotein  
The calculated value of a p-gp-\(I\) descriptor, ranging from 0.000 to 1.000, provided information about the capability of the investigated molecules to inhibit p-gp: the higher the value, the higher the probability to inhibit p-gp [67]. Similarly, the value of a p-gp-S parameter, varying from 0.000 to 1.000, predicted the ability of the analyzed molecules to serve as a substrate for p-gp: the higher the readout, the higher the probability to serve as the p-gp substrates. These calculations were performed by ADMETlab ver. 3.0 [67]. Experimental data referring to the ability of viniferins and vinferin-based compounds to suitably modulate the activity of p-gp are currently not available. The present in silico evaluations showed (Table S4) that a sterically bulky highly lipophilic compound (27) can theoretically act as a moderate inhibitor of p-gp (p-gp-\(I=0.409\)). Thus, this molecule could possibly contribute to the weakening of the multi-drug resistance of bacteria or could help accumulate anticancer agents in the intracellular environment. This might be the way to eventually contribute to the success of anticancer therapy [189]. Other compounds from the (16)-(29) set theoretically showed a lower ability of the p-gp inhibition. The high lipophilicity of (27) was not sufficient for its acting as the p-gp inhibitor. The improved inhibitory activity might be reached if at least one center of protonation, i.e., a tertiary \(N\)-atom, and/or a longer hydrocarbon chain would be appropriately introduced into the structure of the molecule [190]. However, such modifications would definitely affect antibacterial efficacy of the resulting derivatives. The in silico analysis also revealed that the compounds (**16**)-(**29**) should not serve as suitable substrates for a given type of an ATP-binding cassette transporter.