## 3 Results and Discussion
### Combinations of TPZs with Conventional Antibiotics  
The use of combination therapy is commonly justified by the following reasons: to extend the spectrum of drug action (important for heavy infections where early treatment is critical); to prevent or delay the emergence of drug resistance and achieve enhanced (partial or complete synergistic) or at least additive effects, which should allow for the use of a lower dosage of single agents (thereby reducing the risk of their toxic and other side effects) ([14; 31; 32; 33; 48], and refs. therein). Over the past decades, a good deal of work has been done on the anticancer activity of HNOXs, including triapazamine (**1**) and its derivatives in combinations with other antitumor drugs (most notably platinum complexes and alcylating agents) which typically exhibited synergistic or additive effects ([18; 49; 50; 51], and refs. therein). In contrast, to our knowledge, there is no previous research into the combined antimicrobial actions of di-\(N\)-oxides coupled with other drugs, with the exception of the combined study carried out by [PERSON] et al. [14]. This study assessed the activities of quinoxaline di-\(N\)-oxides, including the representative drugs cyadox, mequindox and quinocente with a range of conventional antibacterials towards mycobacteria, mycoplasma and fungi, which at best exhibited additive effects \begin{table}
\begin{tabular}{c c c c c c c c c c} \hline \hline \multirow{2}{*}{**Compound**} & \multirow{2}{*}{**E\({}_{\text{LUMO}}\)**} & \multirow{2}{*}{**E\({}_{\text{HOMO}}\)**} & \multirow{2}{*}{\(\mathbf{x}\)} & \multirow{2}{*}{\(\mathbf{\eta}\)} & \multirow{2}{*}{\(\mathbf{\omega}\)} & \multirow{2}{*}{**log P\({}_{\text{oct}}\)**} & \multirow{2}{*}{**MW/MV**} & \multirow{2}{*}{**PSA**} \\ \cline{3-3} \cline{5-10}  & & & & & & & & & **(Å\({}^{2}\))** \\ \hline TPZ (**1**) & \(-\)3.05 & \(-\)5.93 & 4.49 & 2.88 & 3.50 & 0.75\(\pm\)0.58 & 178.2/157.2 & 72.21 & 1/6 \\ (**2**) & \(-\)3.43 & \(-\)6.34 & 4.89 & 2.91 & 4.10 & 0.63 \(\pm\) 0.60 & 220.2/200.3 & 70.33 & 1/7 \\ (**3**) & \(-\)3.40 & \(-\)6.31 & 4.86 & 2.91 & 4.05 & 1.18 \(\pm\) 0.62 & 234.2/216.4 & 69.74 & 1/7 \\ (**4**) & \(-\)3.29 & \(-\)6.25 & 4.77 & 2.96 & 3.84 & 0.83 \(\pm\) 0.54 & 236.2/207.3 & 76.59 & 1/7 \\ (**5**) & \(-\)3.17 & \(-\)6.13 & 4.65 & 2.96 & 3.65 & 0.55 \(\pm\) 0.31 & 250.2/225.9 & 75.69 & 1/8 \\ (**6**) & \(-\)3.21 & \(-\)6.18 & 4.70 & 2.97 & 3.71 & 1.29 \(\pm\) 0.52 & 250.1/225.9 & 77.60 & 1/8 \\ (**7**) & \(-\)3.63 & \(-\)6.65 & 5.14 & 3.02 & 4.37 & 1.51 \(\pm\) 0.56 & 274.2/212.3 & 69.17 & 1/7 \\ (**8**) & \(-\)3.60 & \(-\)6.64 & 5.12 & 3.04 & 4.37 & 2.81 \(\pm\) 0.83 & 310.2/225.0 & 92.63 & 1/9 \\ (**9**) & \(-\)3.41 & \(-\)6.64 & 5.03 & 3.23 & 3.91 & 2.25 \(\pm\) 0.71 & 256.2/211.0 & 94.03 & 1/9 \\ (**10**) & \(-\)3.51 & \(-\)6.10 & 4.81 & 2.59 & 4.46 & 1.89 \(\pm\) 0.67 & 279.3/256.9 & 63.00 & 2/8 \\ \hline \hline \end{tabular}
\end{table} 
Table 2: The molecular descriptors of TPZs: LUMO (E\({}_{\text{LUMO}}\)), HOMO (E\({}_{\text{HOMO}}\)) energies, global electronegativity (\(x\)), global hardness (\(\eta\)), global electrophilicity (\(\omega\)), molecular weight (MW), molecular volume (MV), octanol/water partition coefficient (Log P\({}_{\text{oct}}\)), polar surface area (PSA), H-bond donor (HBD) and H-bond acceptor (HBA) counts. The Log P values represent the average of the five determinations as described in the Experimental section. against _Mycobacterium tuberculosis_ and _Mycoplasma gallisepticum_ in combination with rifampicin and tetracycline, respectively.