文献类型：期刊文献

英文题名：Novel quinazolin-6-yl Isoindolinone: Altering polysaccharide chemstructure for antibacterial efficacy against Staphylococcus aureus

作者：Huang, Qingchun[1];Zhu, Lisong[1];Huang, Fengcheng[1];Zhao, Yanjun[1];Wang, Hongye[1];Luan, Shaorong[2];Xiao, Ciying[3]

机构：[1]East China Univ Sci & Technol, Sch Pharm, Shanghai Key Lab Chem Biol, Shanghai 200237, Peoples R China;[2]East China Univ Sci & Technol, Sch Chem & Mol Engn, Shanghai 200237, Peoples R China;[3]East China Univ Sci & Technol, Sch Biotechnol, Shanghai 200237, Peoples R China

年份：2024

卷号：280

外文期刊名：INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES

收录：;EI(收录号：20243817070433);WOS:【SCI-EXPANDED(收录号:WOS:001319601900001)】；

基金：This work was sponsored by the projects of Science and Technology Plan of Shanghai Municipal in China (Grant No. 21S11901400, Grant No. 22N41900100) , and the National Natural Science Foundation of China (Grant No. 32372588) .

语种：英文

外文关键词：Quinazolin-6-yl isoindolinone; Antibacterial efficacy; Biofilm formation; Polysaccharide modulation; N -acetylaminoglucosidase; Staphylococcus aureus

摘要：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 mu g mL(-1) and minimal inhibitory concentration (MIC) of 12.5 mu g 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 beta-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.