2,3-bis (phenylamino) quinoxaline - containing compounds display potent activity against Methicillin-resistant Staphylococcus aureus, Enterococcus faecalis and their biofilms

Antimicrobial resistance remains a global challenge threatening the ability to control diseases caused by bacterial infections. Here, we explored the antimicrobial activity of 2,3-N,N-diphenyl quinoxaline derivatives against representative Gram-positive, Gram-negative and Mycobacterium species. Two quinoxaline derivatives (compounds 25 and 31) demonstrated particularly potent activity against most Staphylococcus aureus, Enterococcus faecium and Enterococcus faecalis strains tested (MIC values between 0.25 to 1 mg/l). These compounds also demonstrated potent antibacterial activity against methicillin-resistant S. aureus (MRSA) and vancomycin-resistant E. faecium/E. faecalis (VRE) strains. Against an extensive panel of clinically relevant isolates, they further showed comparable or better activity to four currently used antibiotics (vancomycin, teicoplanin, daptomycin and linezolid). Finally, they performed better in preventing S. aureus and E. faecalis biofilm formation when compared to several other antibiotics. In conclusion, these two quinoxaline derivatives have promising activities that could be further explored as part of efforts to identify urgently needed new antibacterial agents.