## 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 observed distribution of the analyzed compounds (**16**)-(**29**) indicated probable differences in their 'virtual' impact on particular CYP isoenzymes. More comprehensive insight into these relationships is provided in the following paragraphs. The current calculations revealed that all investigated antimicrobials effective molecules (**16**)-(**29**) might function as powerful CYP3A inhibitors (Table S5). Despite the absence of a moiety that acted as a center of protonation, i.e., a functional group containing a tertiary \(N\)-atom, the chemical structure of the analyzed compounds allowed the consideration of such inhibitory ability. The reason was the presence of a condensed furan ring system and, as in the case of the compound (**23**), a triple bond [205]. The predictions should be taken with special care because the inhibitory activity in vivo of these compounds would positively or negatively affect the biotransformation of drugs from various PD groups via the activity of CYP3A [206]. The ADMETlab ver. 3.0 predictor [67] also'suggested' that the molecules (**16**)-(**29**) would not serve as suitable substrates for CYP3A4, CYP2C19, or CYP2B6 (Table S5). The calculations carried out for planar **cis-\(\delta\)-vinifera (16)**, **trans-\(\delta\)-vinifera (17)**, **cis-\(\epsilon\)-viniferin (18)**, **trans-\(\epsilon\)-viniferin (19)**, both derivatives (**24**) and (**28**) containing a planar bicyclic scaffold together with a flexible hydrocarbon chain, methoxylated and halogenated compounds (**26**) and (**27**), as well as for the molecule (**29**) predicted their ability to effectively inhibit both CYP1A2 and CYP2B6 (Table S5). These predictions allowed for their possible utilization as anticancer agents or eventual structural platforms for the design of compounds showing such type of pharmacological activity [207]. This PCA also showed that the increase in log \(D_{7.4}\) (\(r\) = 0.703) and \(tPSA\)\(\leq\) 114.29 A\({}^{2}\) were relatively acceptable trends to describe the predicted CYP1A2 inhibitory efficacy of the (**16**)-(**29**) set (Tables S4 and S6). The calculations met scientific knowledge published  
Figure 14: Two-dimensional observation (mapping) showing both PC 1 and PC 2 scores of the compounds (**16**)–(**29**) following their eventual similarities or differences in the calculated structural and physicochemical descriptors, as well as the in silico ability to affect the CYP isoenzymes. in [208]. On the other hand, inhibition of the CYP1A2 isoenzyme was not only related to anticancer properties of drugs but could be connected with other biological purposes [209]. The planar benzo[_b_]furan bicyclic system that contained no stereogenic center and a flexible ethan-1,2-diyl chain within the compounds (**22**) and (**24**) were convenient structural factors for regarding these derivatives as the substrates for CYP1A2 (Table S5). Both molecules contained hydrogen-bond acceptor groups, were highly lipophilic (Table S3), and were characterized with \(tPSA\) = 114.29 A\({}^{2}\) (Table S4). In fact, an increased \(tPSA\) parameter was only partially related to a higher probability that an analyzed compound could serve as the CYP1A2 substrate (\(r\) = 0.501; Table S6). The introduction of a double or triple bond into a hydrocarbon chain within fragment **D**, as indicated for **dehydro-\(\delta\)-viniferin (20)** in Figure 8, decreased the capability of a compound to serve as a suitable CYP1A2 substrate. The increased lipophilicity (log \(D_{7.4}\)) did not guarantee a higher probability that a molecule would serve as a suitable substrate for CYP1A2 (\(r\) = 0.589). The current findings were in agreement with research [208] concluding that the planar arrangement of both ligand and active site of CYP1A2 was convenient for the oxidation of double bonds or oxidative hydroxylation of large molecules containing aromatic systems. Hydrophobic interactions between ligands and CYP1A2 played central roles in these processes.