Novel quinazolin-6-yl Isoindolinone: Altering polysaccharide chemstructure for antibacterial efficacy against...

The ongoing development of novel strategies to combat Staphylococcus aureus and eliminate its biofilm formation has gained significant attention for human health. Antibiotic-resistant S. aureus necessitates the development of novel antibacterial agents with new mechanism of action. This study introduced a promising recently synthesized quinazolin-6-yl isoindolinone (IQE-X1), which exhibited potent antibacterial and antibiofilm efficacy with average median inhibitory concentration (IC₅₀) of 3.37 μg mL^-1 and minimal inhibitory concentration (MIC) of 12.5 μg mL^-1, coupled with its ability to reduce cell surface hydrophobicity. IQE-X1 dose-dependently decreased extracellular polysaccharides (EPS) and its component monosaccharides, including rhamnose, arabinose, glucosamine, galactose, glucose, xylose, mannose, and ribose, accompanied by an increase in capsular polysaccharides (CP) and its individual monosaccharides, especially glucosamine. IQE-X1 demonstrated specificity in modulating the structural profiles of EPS and CP by altering the compositional ratios of their component monosaccharides. The potential mechanism of polysaccharide modulation was preliminarily elucidated through the response of β-N-acetylaminoglucosidase to IQE-X1 and their direct binding interaction. These findings provide new insights into the potential manipulation of the chemstructure of these biologically important macromolecules, EPS and CP, and highlight the antibacterial potential of IQE-X1 as a polysaccharide modulator for the development of more effective polysaccharide-targeted strategies against S. aureus.