## 3 Biotransformation of Viniferins
### Prediction of Some Parameters That Describe Drug-Likeness
Another synthetic analogue (**28**) of **trans-\(\varepsilon\)-viniferin (19)** containing a flexible ethanol-1,2-diyl chain, which linked two aromatic systems (Figure 11), showed a notable inhibitory impact in vitro on the growth of a Gram-positive _Streptococcus pneumoniae_ strain, and eliminated the bacterium in biofilms [148]. The Gram-positive _L. monocytogenes_ Scott A strain was also chosen to screen the biological potential in vitro of the compounds structurally related to both **dehydro-\(\delta\)-viniferin (20)** and **dehydro-\(\varepsilon\)-viniferin (21)**. In fact, their structural optimization had to be performed  
Figure 11: Chemical structure of the compound (**28**) containing a structurally flexible ethanol-1,2-diyl moiety which was active in vitro against _S. pneumoniae_[148]. The fundamental 2,3-dihydrobenzo[_b_]furan scaffold is indicated by a reddish brown color in its structure, asterisk (*) symbols indicate stereogenic centers. with care, because many of the proposed and synthesized derivatives were inefficient in microbiological experiments [149]. The optimization of flexibility, steric, and lipophilic properties, together with decreased number of OH groups and their bonding to proper positions at aromatic systems within such a modified scaffold, resulted in the derivative (**29**). This compound (Figure 12) fought in vitro the _L. monocytogenes_ Scott A pathogen more effectively (MIC = 8 \(\mu\)g/mL, MBC = 64 \(\mu\)g/mL) than its structural template, **dehydro-\(\varepsilon\)-viniferin (21)**, showing MIC = 16 \(\mu\)g/mL and MBC > 512 \(\mu\)g/mL [149], respectively. Moreover, such structural simplifications that provided the derivative (**29**) did not affect its antiproliferative activity in vitro [150] against several cancer cell lines, i.e., A375 (melanoma), H460 (non-small cell lung cancer), and PC3 (prostate cancer), or a healthy (noncancerous) WS1 cell line, i.e., human normal skin fibroblasts, compared to the impact of **dehydro-\(\varepsilon\)-viniferin (21)** on all of these lines. More recent research [151] also confirmed that hydrogenation of a double bond between C2 and C3 within the structure of **dehydro-\(\varepsilon\)-viniferin (21)**, which provided **trans-\(\varepsilon\)-viniferin (19)**, did not eliminate the efficiency against _L. monocytogenes_ OEK ATCC35152. The observations briefly summarized in the previous paragraphs strongly support the idea to utilize the discussed molecules (Figures 8-12) as promising template compounds in the design and development of antibacterials effective in vivo that could provide beneficial outcomes in the treatment of various infections caused by Gram-positive pathogens. In addition, **dehydro-\(\delta\)-viniferin (20)** was able to inhibit in vitro a specific virulence system of _Yersinia pseudotuberculosis_, a Gram-negative nonhemolytic pathogen that causes severe infection in humans. Therefore, the molecule (**20**) could be considered a suitable structural platform for the design of novel derivatives capable of inhibiting the growth of a given bacterial strain [152]. [PERSON] et al. (2013) investigated several tens of compounds produced by plants and observed that \(\varepsilon\)**-viniferin**, at \(c\) = 10 \(\mu\)g/mL, markedly inhibited in vitro the formation of biofilm due to the activity of _P. aeruginosa_ PA14 (clinical isolate) and PAO1 (laboratory reference strain) as well as enterohemorrhagic Gram-negative _Escherichia coli_ O157:H7 (ATCC43895) [153]. This compound also inhibited the production of \(\alpha\)-hemolysin (known as \(\alpha\)-toxin) by the activity of _S. aureus_[154]. The toxin is involved in the development of sepsis and pneumonia [153,155]. Relationships Between the Predicted Structural, Physicochemical, Pharmacokine, and Toxicological Properties of Chosen Vinfierins and Vinfierin-Based Compounds That Were Very Effective Against Gram-Positive Bacteria