## 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
The average \(\log P\) value around 5.00 could help improve the chances that the investigated molecules would serve as the substrates (Table S4). However, other structural and physicochemical properties were not suitable to be considered for this purpose. The lipophilic properties and \(MW\) were factors positively correlated with the ability of compounds to serve as the P-gp substrates. On the other hand, the sum of (\(n_{\text{OHNH}}\) + \(n_{\text{ON}}\)) negatively contributed to this characteristic [190]. * The binding to plasma proteins The extent to which small molecules (small-molecule drugs) bind to plasma proteins depends on their \(MW\), lipophilicity (\(\log P\)s, \(\log D_{7.4}\)), ionization state (p\(K_{\text{a}}\) values), and aqueous solubility [191]. The presently investigated compounds showed 'virtually' [67] rather notable PPB (Table S4) ranging from 91.18% (**18**) to 98.06% (**28**). These calculations were partially in agreement with research [191] stating that the derivatives with \(MW\) = 500.00-700.00 Da were more than 98.00% bound to these proteins. However, the PPB extent for the molecules defined with \(MW\) = 300.00-500.00 Da was considerably lower. Interestingly, if several compounds with the highest \(PPB\) and \(MW\) < 450.15 Da were excluded from an analysis, i.e., if the molecules (**28**), (**23**) and (**29**) were'removed', the relationship between average \(\log P\) values of the remaining compounds and their \(PPB\)s was rather sufficiently described with a second-order polynomial function, the corresponding Equation (1), and the coefficient of determination (\(R^{2}\)). These characteristics were generated using Microsoft Excel and are provided below. \[PPB=-0.542\times(\text{average }\log P)^{2}+7.785\times(\text{average }\log P)+67.903 \tag{1}\] \[R^{2}=0.800\]  
The observation was in agreement with the predicted ability of various clinically approved drugs to bind to plasma proteins [192]. However, the main limitation of this analysis was that the compounds, which interacted the most closely with plasma proteins, were excluded from the proposed calculation. Lipophilicity was a very notable parameter that affected PPB [191; 193], but it was not an absolutely decisive factor in the current case. The set of the most lipophilic compounds defined with the average \(\log P\) values of 6.70 (**27**), 6.15 (**25**), and 6.03 (**26**), respectively, showed 94.51% \(\leq PPB\leq\) 95.77% (Table S4). These values were not the highest within all calculated \(PPB\)s. For example, less lipophilic derivatives (**28**) and (**23**) were characterized with \(PPB\) of 98.06% and 97.00% (Table S4), respectively. The most positive \(r\) values that described the relationships between lipophilicity and \(PPB\) parameters were 0.487 (MLOGP versus \(PPB\)) and 0.485 (CLOGP 4.0 versus \(PPB\)). The certain but not decisive meaning of lipophilicity for PPB in the present analysis was indirectly confirmed by the observation that increased \(tPSA\), calculated for the entire (**16**)-(**29**) set, was partially related to the decrease in \(PPB\) (\(r=-0.533\)). Taking into account primarily acid-base properties, decreased PPB was observed in the following rank [191]: acidic compounds > neutral molecules > zwitterionic compounds > basic molecules. The presently evaluated compounds were neutral in the physiological environment considering their pK\({}_{\text{a}}\)s (Figures S2-S15). Therefore, this factor might contribute to relatively high \(PPB\) outputs (Table S4). * The impact on the cytochrome P450 isoenzymes The CYP hemoprotein isoenzyme superfamily system participates in many key processes required for the maintenance of physiological conditions in the human body [194]. The particular CYP isoenzymes (for example, CYP3A4) are notably involved in the biotransformation of a wide palette of endogenous molecules, many xenobiotics, that is, exogenous compounds, including drugs, as well as in the bioactivity pathways of various entities related to cancer (procarcinogens) [195; 196].