# Recent Updates on the Synthesis of Bioactive Quinoxaline-Containing Sulfonamides
## 2 Synthesis and Biological Activities
### Quinoxaline Sulfonamides with Antibacterial Activity
In this synthetic strategy, the nucleophilic substitution was performed by attacking the electrophilic center (S) of chloro sulfonic acid **47** by the benzene of diphenyl quinoxaline **56** to furnish the intermediate 2,3-diphenylquinoxaline-6-sulfonyl chloride **57**, which further refluxed with the substituted primary amine under basic conditions to deliver the final product diphenyl quinoxaline sulfonamide **58** in moderate to good (69-83%) yield (Scheme 3). The aromatic amines with EWG, such as nitro, lead to the final products in a higher yield, while the aromatic amines with EDG, such as methyl and methoxy, etc, lead to final products in low yield [129]. The quinoxaline sulfonamide analogs **59** displayed the highest antibacterial activity, exhibiting a ZOI value of 10 mm against _S. aureus_ and 8 mm against _E. coli_ at a concentration of 100 \(\upmu\)g (microgram), while the quinoxaline sulfonamide hybrid **60** showed moderate antibacterial activity, with a ZOI of 7 mm and 6 mm at a concentration of 100 \(\upmu\)g against _S. aureus_ and _E. coli_, respectively (Table 3). The moderate antibacterial activity was observed for derivative **61** that exhibited a ZOI value of 6 mm against _S. aureus_ at a concentration of 100 \(\upmu\)g, and derivative **62** exhibited the least antibacterial activity by inducing a 2 mm ZOI value at the concentration of 100 \(\upmu\)g against _E. coli_, when compared with the standard drug azithromycin (ZOI value of 12 mm and 10 mm against _S. aureus_ and _E. coli_ at the concentration of 100 \(\upmu\)g). The SAR revealed that the maximum antibacterial activity was observed in the presence of a strong EWD group (chloro atom) on the ring of analogue **59**, while the introduction of a _m_-OH and _p_-OH group on the ring produced a moderate activity for compounds **60** and **61**. The derivative **62** exhibited the least antibacterial activity due to the presence of an electron-denoting methoxy group at the phenyl ring (Figure 9). The presence of EWG showed the highest antibacterial activity as compared to the presence of EDG, which displayed moderate to low antibacterial activity [129]. Figure 8: Substituted quinoxaline benzene sulfonamide derivatives **50–55**. [PERSON] and coworkers developed a novel synthetic strategy for the synthesis of indole-based quinoxaline sulfonamides. These sulfonamide derivatives were evaluated for their antimicrobial activity against different bacterial and fungal strains. Indole quinoxaline ana  
Figure 9: Substituted quinoxaline sulfonamide derivatives 59–62. \begin{table}
\begin{tabular}{c c c} \hline \hline \multirow{2}{*}{**Compound**} & \multicolumn{2}{c}{**Zone of Inhibition (mm) at 100 \(\upmu\)g**} \\ \cline{2-3}  & \multicolumn{2}{c}{_S. aureus_} & _E. coli_ \\ \hline
59 & 10 & 8 \\
60 & 7 & 6 \\
61 & 6 & 7 \\
62 & 9 & 2 \\ Azithromycin & 12 & 10 \\ \hline \hline \end{tabular}
\end{table} 
Table 3: Antibacterial activity of quinoxaline-based substituted benzene sulfonamide derivatives. logue **64** was afforded by the reaction of OPD **34** with 5-bromoisatin **63** heated to reflux for 30 min. The scaffold **64** was refluxed with chlorosulfonic acid **47** to obtain the quinoxaline sulfonyl chloride **65** that was further treated with substituted amines in anhydrous acetone and pyridine to furnish final quinoxaline sulfonamides **66** via dehydrohalogenation in a low to moderate (20-47.5%) yield (Scheme 4) [130]. Some of the synthesized quinoxaline sulfonamide derivatives were screened for antimicrobial activities against some bacterial and fungal strains. The quinoxaline sulfonamide **67** showed the most potent antibacterial and antifungal activity, with ZOI values of 14 mm, 14 mm, 16 mm, 17 mm and 17 mm against _S. aureus_, _B. pimilis_, _E. coli A. niger_ and _P. notatum_, respectively at 50 \(\mathrm{\SIUnitSymbolMicro g}\)/mL (Table 4). The quinoxaline sulfonamide derivative **68** demonstrated a moderate activity, exhibiting ZOI values of 13 mm against _S. aureus_, 14 mm against _B. pimilis_, 15 mm against _E.