# Recent Updates on the Synthesis of Bioactive Quinoxaline-Containing Sulfonamides
## 2 Synthesis and Biological Activities
### Quinoxaline Sulfonamides with Antibacterial Activity  
[PERSON] et al. reported a facile, efficient, solvent and catalyst-free green protocol for the synthesis of quinoxaline sulfonamide derivatives, which were screened for their antibacterial activity against different Gram-positive and Gram-negative bacterial strains. The quinoxaline sulfonyl chloride (QSC) **48** was synthesized in 85% yields by the treatment of methoxyphenyl quinoxaline **46** with chlorosulfonic acid **47**. The QSC scaffold **48** was reacted with substituted aromatic amines in neat and ecofriendly conditions to afford substituted quinoxaline sulfonamides of the type **49** in good to excellent yield (Scheme 2). \begin{table}
\begin{tabular}{c c c c} \hline \hline
**Compound** &
\begin{tabular}{c} **Urinary Accretion** \\ **Percentage** \\ \end{tabular} & **Diuretic Activity** & **Lipschitz Value** \\ \hline
43 & 176.66 & 1.13 & 1.28 \\
44 & 121.42 & 0.78 & 0.88 \\
45 & 87.5 & 0.56 & 0.63 \\ Acetazolamide & 155.17 & 1.0 & 1.13 \\ Urea & 136.6 & 0.88 & 1.0 \\ \hline \hline \end{tabular}
\end{table} 
Table 1: Diuretic activity of benzothiazole quinoxaline sulfonamide derivatives **43–45**. Figure 7: Substituted quinoxaline benzothiazole sulfonamide derivative **43–45**. Aromatic amines with EDG, such as methyl and methoxy, reacted in 3-10 min and lead to products with a higher yield, while aromatic amines with EWG afforded products with a low yield. Aromatic amines with strongly EWG, such as nitro, do not react in the below mentioned conditions [128]. The substituted 4-methoxyphenyl quinoxaline sulfonamide **50** and substituted 2-methoxy quinoxaline sulfonamide derivative **51** showed the best antibacterial activity against _S. Aureus_, having a zone of inhibition (ZOI) of 20 mm and 22 mm, respectively, which is more than the standard chloramphenicol drug (ZOI 19 mm) but less than reference ampicillin drug (ZOI 28 mm). The substituted naphthalene quinoxaline sulfonamide derivatives **52** exhibited the highest antibacterial activity against _E. coli_, with a ZOI value of 18 mm when compared to the standard drug, ampicillin (ZOI 15 mm), but less than the reference chloramphenicol drug (ZOI 19 mm) (Table 2). A moderate antibacterial activity was observed for the substituted chlorophenyl quinoxaline sulfonamides **53** and **54** against Gram-positive _S. Aureus_ and Gram-negative _E. coli_. The unsubstituted phenyl quinoxaline sulfonamide derivative **55** showed the least antibacterial activity against _S. Aureus_ and _E. coli_, exhibiting a ZOI of 5 mm and 5>_ mm, respectively, when compared to the reference drugs, chloramphenicol and ampicillin, exhibiting ZOI values of 19 mm and 28 mm against _S. Aureus_ and 22 mm and 15 mm against _E. coli_. The SAR revealed that the presence of electron-rich groups on the aminophenyl ring showed the highest antibacterial activity for derivatives **50-52**, whereas the presence of the electron-withdrawing groups on the aminophenyl ring, such as a chloro atom (weak EWD group), in **53** and **54** scaffolds led to a moderate antibacterial activity, while the least antibacterial activity was observed for the unsubstituted derivative **55** (Figure 8) [128]. The results showed that electron-donating group's substitution on the quinoxaline sulfonamide scaffolds contribute positively to increase the antibacterial activity. \begin{table}
\begin{tabular}{c c c} \hline \hline \multicolumn{3}{c}{**Antibacterial Activity (DMSO, 4 mg mL\({}^{-1}\))**} \\ \hline \multirow{3}{*}{**Compound**} & **Diameter of Zone of Inhibition (mm)** \\ \cline{2-3}  & _S. Aureus_ & _E. coli_ \\ \hline
50 & 20 & 9 \\
51 & 22 & 11 \\
52 & 17 & 18 \\
53 & 15 & 12 \\
54 & 11 & 13 \\
55 & 5 & 5> \\ Chloramphenicol & 19 & 22 \\ \hline \hline \end{tabular}
\end{table} 
Table 2: Antibacterial activity of quinoxaline benzene sulfonamide derivatives **50–55**. [PERSON] et al. synthesized antimicrobial quinoxaline sulfonamide derivatives by applying a convenient and an expeditious methodology.