# Recent Updates on the Synthesis of Bioactive Quinoxaline-Containing Sulfonamides
## 2 Synthesis and Biological Activities
### Quinoxaline Sulfonamides with Antibacterial Activity
coli_ and 12 mm against _A. niger_ at 50 \(\mathrm{\SIUnitSymbolMicro g}\)/mL. The derivative **69** exhibited the lowest ZOI values of 10 mm against _B. pimilis_ and 10 mm against _A. niger_ at 50 \(\mathrm{\SIUnitSymbolMicro g}\)/mL. The reference standard streptomycin at 50 \(\mathrm{\SIUnitSymbolMicro g}\)/mL exhibited a ZOI of 18 mm, 20 mm and 20 mm against _S. aureus_, _B. pimilis_ and _E. coli_ strains, respectively. Micronazole nitrate exhibited, instead, 23 mm and 20 mm ZOI values at 50 \(\mathrm{\SIUnitSymbolMicro g}\)/mL against _A. niger_ and _P. notatum_ strains. The SAR showed that the introduction of a bromophenyl moiety on the sulfonamide increased the antimicrobial activity of **67**, while thioamide functionality was incorporated in analogue **68** to induce a moderate antimicrobial activity. The acetophenone moiety-containing derivative **69** displayed the least antimicrobial activity (Figure 10). The SAR study indicated that the antimicrobial activity decreased in the order Bromo > Thiamide > Acetyl. The results in the Table 4 showed that the structural motif **67** displayed a broad spectrum antimicrobial therapeutic potential against different bacterial and fungal strains than the reference standard drugs [130]. \begin{table}
\begin{tabular}{c c c c c c} \hline \hline \multirow{3}{*}{**Compound**} & \multicolumn{5}{c}{**Zone of Inhibition (mm)**} \\ \cline{2-6}  & \multicolumn{3}{c}{**Antibacterial**} & \multicolumn{3}{c}{**Antifungal**} \\ \cline{2-6}  & _S. aureus_ & _B. pimilis_ & _E.coli_ & _A. niger_ & _P. notatum_ \\ \hline
67 & 14 & 14 & 16 & 17 & 17 \\
68 & 13 & 14 & 15 & 12 & - \\
69 & - & 11 & - & 10 & - \\ Streptomycin & 18 & 20 & 20 & - & - \\ Micronazole & - & - & - & 23 & 20 \\ nitrate & & & & & \\ \hline \hline \end{tabular}
\end{table} 
Table 4: Antimicrobial activity of quinoxaline-substituted benzene sulfonamide derivatives **67–69**. An efficient pathway was adopted by [PERSON] et al. to afford substituted quinoxaline sulfonamide derivatives, and they analyzed these designed scaffolds for antibacterial therapeutic potential by the agar diffusion method. The 1,4-dihydroquinoxaline-2,3-dione (**71**) was prepared by condensation of **34** with oxalic acid **70**. In the next step, reaction with chlorosulfonic acid (**47**) at 0-5 \({}^{\circ}\)C furnished the quinoxaline scaffold with chlorosulfonyl moiety **72**, which was combined with different amino compounds, such as amines, amino acids, morpholine and piperazine, to produce final quinoxaline sulfonamide derivatives **73** in good yield (61-66%) (Scheme 5) [131]. The quinoxaline sulfonamide **74** displayed the highest antibacterial activity, with a zone of inhibition (ZOI) of 15 mm and 10 mm against _S. aureus_ and _E. coli_, respectively, while the reference drug, sulfadiazine, gave a ZOI of 14 mm and 13 mm zone diameter against _S. aureus_ and _E. coli_ (Table 5). The derivative **75** showed equipotent antibacterial activity (ZOI of 14 mm) against _S. aureus_ in comparison with the reference drug (ZOI of 14 mm), but less antibacterial activity (ZOI of 8 mm) against _E. coli_ than the reference drug (ZOI of 13 mm). A moderate activity was observed for the quinoxaline sulfonamide derivative **76** that led to a ZOI of 12 mm and 10 mm against _S. aureus_ and _E. coli_, respectively. Compound **77** exhibited the lowest antibacterial activity, showing a ZOI of 10 mm against _S. aureus_ with respect to the reference drug sulfadiazine, but it did not exhibit any activity against _E. coli_. The SAR studies demonstrated that the presence of a propanol or benzoic acid moiety on the sulfonamide analogs **74** and **75** displayed an excellent and slightly higher or equipotent antibacterial activity in comparison with the reference drug sulfadiazine,  
Figure 10: Substituted quinaxoline sulfonamide derivatives **67–69**. while the presence of a sulfonyl glycine moiety was responsible for the moderate activity of the derivative **76**.