## 3 Biotransformation of Viniferins
### Prediction of Some Parameters That Describe Drug-Likeness
#### 5.2.4 Predicted Toxicological Properties of Chosen Viniferins and Viniferin-Based Compounds  
The SwissADME tool [66] indicated that the presently considered derivatives **(16)-(29)** contained no electrophilic group(s), which theoretically would be responsible for the nonselective interactions of these compounds with several pharmacological targets. The class of molecules that showed such properties was termed pan-assay interference compounds [217]. The predictor [66] also contained a database compiled from the series of fragments, previously identified by [PERSON] et al. [218], which could cause toxicity, chemical reactivity, or metabolic instability. The fragments could also be responsible for inconvenient PK properties. The compounds **(16)-(21)**, **(23)**, **(25)-(27)**, and **(29)** contained one alert, a stilbene moiety. One alert, the triple bond, was also present in the structure of the compound **(23)**. Therefore, the next step in the evaluation of the molecules **(16)-(29)** was the in silico analysis of their toxicological properties, also in relation to structural and physicochemical characteristics. The preliminary view on the eventual similarities or differences in their selected in silico structural and physicochemical descriptors, i.e., \(MW\), \(MR\), \(V_{\mathrm{vdW}}\), flexibility, MLOGP, CLOGP 4.0, WLOGP, ALOGPS, XLOGP3, miLogP 2.2, log \(D_{7.4}\), \(tPSA\) (Tables S2-S4), and the impact on the 'virtual' DILI, H-HT, DINf, OT, DINe, and nERG properties (Tables S7 and S8) showed a certain grouping of the compounds **(16)-(29)**. The positive information was that the entire set of these derivatives was visualized in the constructed coordinate system of PC 1 and \(\times\) PC 2 (Figure 15). The PCs accounted for 81.61% of the total variance in the data as follows: PC 1 (54.53%, \(\lambda_{\mathrm{e}}=9.82\)) and PC 2 (27.08%, \(\lambda_{\mathrm{e}}=4.87\)). The details about this PCA are provided in Supplementary Materials. The compounds **(16)-(19)** were characterized with both negative PC 1 and PC 2, the derivatives **(20)-(24)** and **(29)** were defined with negative PC 1 and positive PC 2. The molecules **(28)** and **(26)** were described with positive PC 1 and negative PC 2, and finally, the compounds **(25)** and **(27)** were defined by both positive PC 1 and PC 2. The derivative **(27)** seemed to be'slightly isolated'. More comprehensive insights into these relationships are provided in the following paragraphs. DILI, a form of idiosyncratic toxicity that occurs very frequently in humans, could seriously damage patients' health and might be the main cause for withdrawal of already clinically approved drugs [219; 220]. The in silico _DILI_ indicator, generated within an interval from 0.000 to 1.000 [67], showed a compound without risk of DILI (_DILI_ relatively close to 0.000), medium risk of DILI (_DILI_ around 0.500), or with a high risk of DILI (_DILI_ relatively close to 1.000). The possible threat was also color-coded [67]; a green color indicated no risk, an orange color predicted a medium risk, and finally a red color was the indicator for a highly risky molecule (Table S7). The values of a calculated _DILI_ parameter (Table S7) did not show a risk of DILI for the compounds (**16**)-(**19**), (**24**), and (**28**), and suggested a medium DILI risk for the molecules (**20**)-(**23**), (**25**)-(**27**), and (**29**). The results of this PCA also indicated that an increased adverse DILI effect of the evaluated compounds relatively notably positively correlated with the increase in their lipophilicity (Table S8). The lipophilicity descriptors, for which attention should be primarily paid in that regard, were WLOGP (\(r\) = 0.708), log \(D_{7.4}\) (\(r\) = 0.686), and miLogP 2.2 (\(r\) = 0.611). These observations supported the findings and conclusions already published in [221, 222]. This paper also focused on the exploration of eventual medium or even high risk of hepatotoxicity, described with the \(H\)-\(HT\) parameter, for the compounds (**16**)-(**29**).