## 3 Biotransformation of Viniferins
### Prediction of Some Parameters That Describe Drug-Likeness
#### 5.2.1 General Overview
It should be emphasized that the respective PCs did not prove the existence of'real' structural or physicochemical parameters; they only indicated the mathematical possibility that such descriptors existed [157]. The interpreted PC 1 and PC 2 accounted for 81.15% of the total variance in the current data (PC 1: 59.34%, PC 2: 21.81%). The calculated eigenvalue (\(\lambda_{\text{e}}\)) parameters [157] were the following: 14.24 (for PC 1) and 5.24 (PC 2). The details about this PCA with brief definitions of several fundamental terms are provided in Supplementary Materials. The compounds (**25**)-(**27**) were characterized with both negative PC 1 and PC 2, and (**27**) was visually'slightly isolated'. The molecules (**20**) and (**24**) were defined with negative PC 1 and positive PC 2, and, in addition, were relatively close to two miniseries (**16**)-(**19**) and (**21**)-(**23**) defined with both positive PC 1 and PC 2. The compounds (**28**) and (**29**) were visually 'isolated' and defined with positive PC 1 and negative PC 2. Therefore, such a distribution of the molecules (**16**)-(**29**) indicated differences in the structural and physicochemical parameters generated. The more comprehensive insight into those relationships is provided in the following paragraphs. Molecular weight, fraction of \(sp^{3}\) carbon atoms, molecular refractivity, and van der Waals volume  
All compounds currently discussed **(16)-(29)** were so-called small molecules (potential small-molecule drugs, eventually) with \(MW\)! 900.00 Da **(158)**. This threshold value would not be taken so strictly because the cut-off limit to define a pharmacologically active compound as a small-molecule drug could be evaluated from different aspects. For example, [PERSON] et al. [120] suggested the limit of \(MW\)! 480.00 Da and [PERSON] et al. [159] used \(MW\)! 1500.00 Da as the upper value. The \(MW\) values of evaluated compounds **(16)-(29)** ranged from 344.10 Da **(29)** to 550.09 Da **(27)**; most of them had \(MW\)! 454.14 Da (Table S2), and an average \(MW\) parameter for the entire set of molecules was 458.41 Da. Following the very strict rule [120], only synthetic derivatives **(22)**, **(28)**, and **(29)** could be potential small-molecule drugs. However, such a rigorous limit may not be taken into account to absolute extent, and \(MW\)! 900.00 Da **(158)** to fulfill a given condition seemed to be more reasonable. [PERSON] [160] concluded that the distribution of effective antibacterial agents biologically available per os was bimodal. The first group of these molecules was characterized with \(MW\) = 350.00-450.00 Da, and the second group, including several antibiotics, had \(MW\) = 700.00-900.00 Da [160]. The \(MW\) values around 450.00 Da favored the majority of presently analyzed derivatives as eventual therapeutic agents, which could be administered per os [160] to combat infections caused by Gram-positive bacteria as listed in Section 5.1. Moreover, these molecules were defined with \(MW\)! 414.00 Da and log \(D_{7.4}\)! 2.40 (Table S2) so that their improved permeability might be expected. The compounds with \(MW\)! 414.00 Da and log D\({}_{7.4}\)! 1.30 also showed higher permeability [161]. Other relevant connections between \(MW\) and predicted PK, as well as toxicological characteristics, are discussed in the following paragraphs. The \(MW\) parameter might be less relevant to describe a drug-like profile of pharmacologically active molecules or drug candidates compared to the significance of their  
Figure 13: Two-dimensional observation (mapping) showing both Principal Component 1 (PC 1) and PC 2 scores of the compounds **(16)–(29)** following their eventual similarities or differences in the calculated structural and physicochemical descriptors. conformational properties [117]. The compounds (**16**)-(**29**) contained only C2 and C3 atoms as possible centers of chirality depending on the presence or absence of a double bond within their five-membered ring and selection of particular substituents (Figures 8-12, Table S2).