Compounds Containing 2,3‐Bis(phenylamino) Quinoxaline Exhibit Activity Against Methicillin‐Resistant <i>Staphylococcus aureus</i>, <i>Enterococcus faecalis</i>, and Their Biofilms

Antimicrobial resistance remains a global issue, hindering the control of bacterial infections. This study examined the antimicrobial properties of 2,3-N,N-diphenyl quinoxaline derivatives against Gram-positive, Gram-negative, and Mycobacterium species. Two quinoxaline derivatives (compounds 25 and 31) exhibited significant activity against most strains of Staphylococcus aureus, Enterococcus faecium, and Enterococcus faecalis tested, with MIC values ranging from 0.25 to 1 mg/L. These compounds also showed effective antibacterial activity against methicillin-resistant S. aureus (MRSA) and vancomycin-resistant E. faecium/E. faecalis (VRE) strains. They demonstrated comparable or superior activity to four current antibiotics (vancomycin, teicoplanin, daptomycin, and linezolid) against a wide range of clinically relevant isolates. Additionally, they were more effective in preventing S. aureus and E. faecalis biofilm formation compared to several other antibiotics. In summary, these two quinoxaline derivatives have potential as new antibacterial agents.