## 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 hemoproteins that participate in the activation of procarcinogens via different mechanisms are especially CYP1A1, CYP1A2, CYP1B1, CYP2A6, CYP2A13, and CYP2E1 [196; 197]. The significance of knowing about eventual inhibitory activity of the various exogenous ligands, that is, viniferins and their derivatives in this case, toward particular CYP isoenzymes, or about possible induction of these biomolecules could be illustrated by several examples from clinical practice. The biotransformation in vivo of the clinically approved drugs, which were already mentioned, was dependent on the activity of particular CYP isoenzymes. The inhibitors or inducers of these hemoprotein biomolecules could markedly affect the extent of metabolism of respective drugs. **Amiodarone (8)** is oxidatively \(N\)-deethylated via the activity of CYP3A4 providing two potentially life-threatening hepatotoxic metabolites [198]. **Vilazodone (9)** is biotransformed primarily by a given isoenzyme and secondarily by CYP2C19 and CYP2D6 [199; 200]. The inhibition of CYP3A4 significantly decreases the dosage of this antidepressant [201]. The CYP3A4/5 and CYP1A2 isoenzymes are mainly responsible for extensive biotransformation of **tasimleton (11)**[202], and powerful inhibitors or inducers of these isoenzymes notably affect its PK properties [203]. **Darifenacin (14)** is metabolized through the CYP3A4 and CYP2D6 pathways, and effective inhibitors or inducers of both CYP3A4 and CYP2D6 show a significant impact on **darifenacin's (14)** biotransformation [204]. The preliminary view on eventual similarities or differences of the antibacterially effective compounds **(16)-(29)** in their in silico structural and physicochemical descriptors, i.e., _MW_, _MR_, \(V_{\text{vdW}}\), flexibility, MLOGP, CLOGP 4.0, WLOGP, ALOGPS, XLOGP3, miLogP 2.2, log \(D_{7,4}\), _tPSA_ (Tables S2-S4), and PK (biochemical) parameters, is provided in Figure 14. The PK (biochemical) characteristics of **(16)-(29)** are represented by the CYP1A2-_I_, CYP1A2-S_, CYP2C19-_I_, CYP2C9-_I_, CYP2C9-_S_, CYP2D6-_I_, CYP2D6-_S_, and CYP2B6-_I_ indices (Tables S5 and S6) related to their in silico inhibitory activity (_I_ letter is listed in the name of a particular parameter) or the 'virtual' ability to serve as the substrates for respective enzymes (_S_ letter). The values of the given parameters might vary from 0.000 to 1.000 (Table S5). The impact of the compounds **(16)-(29)** on particular isoenzymes was evaluated with respect to the following criteria: no inhibitory activity or no substrate (values of particular descriptors were relatively close to 0.000), moderate inhibitory activity or moderate capability to serve as a substrate (values of individual parameters were around 0.500), and notable inhibitory activity or a very suitable substrate (values of particular descriptors were relatively close to 1.000). All the compounds **(16)-(29)** could be found in the constructed coordinate system of PC 1 \(\times\) PC 2 (Figure 14), and they showed certain groupings or relative 'isolation'. The PCs accounted for 70.83% of the total variance in the data as follows: PC 1 (46.78%, \(\lambda_{\text{e}}\) = 9.36) and PC 2 (24.05%, \(\lambda_{\text{e}}\) = 4.81). The details about this PCA are provided in Supplementary Materials. The rank of the considered molecules was based on the combination of PC 1 and PC 2 starting with the derivatives with the lowest PC 1. The compounds **(29)**, **(17)**, **(16)**, **(18)**, **(19)**, and **(28)** were characterized with both negative PC 1 and PC 2, the derivatives **(22)**, **(23)**, **(21)**, and **(20)** were defined with negative PC 1 and positive PC 2. The molecule **(24)** was close to the latter set and was characterized with both positive PC 1 and PC 2. The compound **(25)** was described with both positive PC 1 and PC 2, and finally the derivatives **(26)** and **(27)**were defined with positive PC 1 and negative PC 2. In addition, the compounds (**27**) and (**28**) were visually'slightly isolated' (Figure 14).