Introduction: The ability of Staphylococcus aureus  to form biofilms is associated with high mortality and treatment costs. Established biofilms cannot be eradicated by many conventional antibiotics due to the development of antibiotic tolerance by S. aureus . Here we report the synthesis and biological characterization of novel small-molecule compounds with antibiofilm activity. Chromone 5-maleimide substitution compounds (CM3a) showed favorable antibacterial activity against S. aureus .
Methods: CM3A with antibacterial activity was synthesized and screened. The minimum inhibitory concentration (MIC) of CM3a were determined by the broth microdilution method. Biofilm eradication assay and colony count methods were used to investigate the effect of CM3a on S. aureus  biofilm disruption and killing. Changes in biofilm architecture when subjected to CM3a, were visualized using confocal laser scanning microscopy (CLSM). CCK-8 assay and survival rate of Galleria mellonella  larvae were used to test the toxicity of CM3a.
Results: The minimum inhibitory concentration (MIC) of CM3a against S. aureus  was about 26.4 μM. Biofilm staining and laser scanning confocal microscopy analysis showed that CM3a eradicated S. aureus  biofilms by reducing the viability of the constituent bacterial cells. On the other hand, CM3a showed negligible toxicity against mouse alveolar epithelial cells and Galleria mellonella  larvae.
Conclusion: Chromone derivatives CM3a has therapeutic potential as a safe and effective compound for the treatment of S. aureus  infection.
Keywords: chromone derivative, maleimide, Staphylococcus aureus , biofilm, eradicate