## 3 Biotransformation of Viniferins
### Prediction of Some Parameters That Describe Drug-Likeness
#### 5.2.4 Predicted Toxicological Properties of Chosen Viniferins and Viniferin-Based Compounds
The values of the _HeT_ index, ranging from 0.003 (two naturally occurring viniferins) to 0.060 (27), allowed one to consider none of the compounds **(16)-(29)** hematotoxic (Table S7). Some effective antibacterial drugs belonging to an aminoglycos antibiotic class or nonaminoglycos antibiotics, i.e., vancomycin, which was already mentioned, negatively affect cochlea or vestibular apparatus located within the inner ear. The consequence may be a very serious health issue, loss of hearing [230; 231]. Although **RSV (1)** has been reported to alleviate the causes of **cis-platin**-induced ototoxic effects in experiments under conditions in vitro through various protective mechanisms [232] and **2,3,4,5-tetrahydrooxystilbene-2-\(O\)-\(\beta\)-D-glucose** attenuated ototoxic manifestations triggered by gentamicin [233], the prediction of the values of \(OT\), which was related to possible ototoxicity, provided more diverse conclusions. The \(OT\) descriptor calculated for **(16)-(29)** might be found in the interval from 0.000 to 1.000. The rules for the appropriate color-coding of their safe versus risky behavior were the same as for _DILI_ (Table S7). The present evaluation indicated that only six compounds from the **(16)-(29)** set 'virtually' showed no risk of ototoxicity, i.e., the molecules **(20)-(24)** and **(29)** defined with \(OT\leq 0.282\). On the other hand, the most ototoxic derivatives were characterized with \(OT\geq 0.744\) (Table S7). The ototoxic properties of the evaluated compounds **(16)-(29)** partially positively correlated with MLOGP (\(r\) = 0.708), flexibility (\(r\) = 0.635), and \(V_{\rm vdW}\) (\(r\) = 0.617). The _tPSA_ parameter had only a lower significance (\(r\) = \(-\)0.335). However, the contribution of lipophilicity to ototoxicity was not absolutely clear because a negative correlation with log \(D_{7,4}\) was generated (\(r=-0.509\); Table S7). Possible neurotoxic effects of various antibacterial chemotherapeutics, antimyobacterial and antileprosy drugs, or antiparasitic agents have been known and reported in the past decades of the previous century [234], and research on the neurotoxic features of these compounds continues [235]. Paradoxically, attention is also focused on the utilization of selected antibacterial chemotherapeutics (for example, **minocycline**, an antibiotic molecule chemically belonging to a tetracycline class) as neuroprotective agents [236; 237]. The _DINe_ parameter related to possible neurotoxicity was another feature calculated for **(16)-(29)**. This descriptor might be found in the interval from 0.000 to 1.000. The rules for the appropriate color-coding of the compounds following their safe versus risky behavior were the same as for _DILI_ (Table S7). The highest risk of neurotoxicity was theoretically related to naturally occurring **cis-\(\delta\)-viniferin (16)**, **cis-\(\epsilon\)-viniferin (18)**, as well as synthetic derivatives **(25)-(27)**. These molecules were characterized with _DINe_\(\geq\) 0.734. The lowest potential to induce neurotoxic processes was predicted for the compound **(23)** with _DINe_ = 0.052 (Table S7). The relationships between the generated structural as well as physicochemical descriptors and _DINe_ would not be possible to define as linear due to the relatively low \(r\) values (Table S8). The non-CV drug-induced blockade of a potassium channel, which is encoded by hERG, caused prolongation of a QT interval, resulting in even fatal sudden cardiac death. Therefore, the regulatory authorities decided to withdraw already approved drugs showing such undesirable properties, for example, **terfenadine** acting as an antihistamine drug or antibacterially effective **grepafloxacin**, from pharmaceutical markets worldwide as a very reasonable response to concerns about cardiac safety and the occurrence of such fatal cases [238; 239; 240]. The ability to induce long-QT syndrome (LQTS) was also observed for **amiodarone (8)**[241]. On the other hand, **RSV (1)** showed beneficial antidysrhythmic activity in acquired LQTS [242].