## 3 Biotransformation of Viniferins
### Prediction of Some Parameters That Describe Drug-Likeness
aureus_ described with estimated values of a minimum inhibitory concentration (MIC) of 16 \(\mu\)g/mL for both compounds (**17**) and (**21**), as well as with MIC = 2 \(\mu\)g/mL for molecule (**20**). Moreover, thedehydrogenated NP (**20**) induced the death of _S. aureus_ cells at a relatively low minimal bactericidal concentration (MBC) of 16 ug/mL [138]. Anti-staphylococcal efficiency in vitro of both dimers (**17**) and (**19**) was also supported by previous conclusions [139,140]. The presence of a lipophilic styryl moiety and even a double bond in an acyclic hydrocarbon chain of the **D** compartment (Figure 8) of **dehydro-\(\delta\)-viniferin (**20**) were not the mandatory structural requirements to maintain the activity in vitro [141] of a given molecule against _S. aureus_ ATCC29213. The proper modifications of both **A** and **D** fragments, including the introduction of a triple bond or a short lipophilic hydrocarbon chain, were mirrored in the design and synthesis of antimicrobials efficient molecules (**22**)-(**24**), and their structures are also provided (Figure 9). The estimated MICs and MBCs for particular compounds when tested against _S. aureus_ ATCC29213 were the following: MIC = 4 ug/mL, MBC \(\geq\) 512 ug/mL (**22**), MIC = 2 ug/mL, MBC = 8 ug/mL (**23**), and MIC = MBC = 4 ug/mL (**24**), respectively. The screened derivatives (**22**)-(**24**) were more promising than a **dehydro-\(\delta\)-viniferin (**20**) reference compound showing MIC = 2 ug/mL and MBC \(\geq\) 512 ug/mL, respectively. Figure 8: Chemical structure of dehydrogenated viniferins, i.e., **dehydro-\(\delta\)-viniferin (**20**) and **dehydro-\(\epsilon\)-viniferin (**21**), antibacterially screened in vitro [138]. The fundamental benzo[\(\phi\)]furan scaffold is indicated by a green color in the structure of both compounds. The **A–D** letters indicate particular structural compartments of the molecule (**20**). In fact, there was enough room to improve the antimicrobial efficacy of **trans-\(\delta\)-viniferin (17)**-derived molecules. Taking this idea in mind, the plant metabolite (17) was used as a suitable'starting structural template' for the design, synthesis, and screening in vitro of several tens of derivatives employing an isomerization, \(O\)-methylation, halogenation, and dimerization strategy [142]. The purpose of such modifications was not only to'simply' improve PD but also to optimize structural, physicochemical, and PK properties of proposed molecules. These derivatives (Figure 10) fought the screened bacteria more effectively than standard drugs, i.e., **trans-\(\delta\)-viniferin (17)** and vancomycin, a structurally complex hydrophilic glycopeptide antibiotic that contains a tricyclic system, isolated from _Streptomyces orientalis_. Thus, the prepared structural analogues (Figure 10) of the compound (17) were tested in vitro against two \(S\). _aureus_ strains, i.e., Newman (methicillin-susceptible _S. aureus_; _MSSA_) and COL (methicillin-resistant _S. aureus_; _MRSA_) [142]. Simultaneous \(O\)-methylation of precisely chosen OH group(s) and introduction of halogen atoms into the proper positions of particular aromatic systems were beneficial structural modifications, which improved antibacterial activity of the resulting chlorinated compounds (25)-(27). The estimated MIC values for (25)-(27) against _MSSA_ were as follows: 0.5-1.0 \(\mu\)g/mL (25), 1 \(\mu\)g/mL (26), and 1-2 \(\mu\)g/mL (27). The efficiency of the most active derivatives against _MRSA_ was described with MICs of 1 \(\mu\)g/mL (26) and 0.6-1 \(\mu\)g/mL (27). The inhibitory effect of all of these molecules against _MSSA_ was higher compared to the activity of **trans-\(\delta\)-viniferin (17)** and very comparable to the inhibitory activity of vancomycin [142].