文献类型： 外文期刊
作者： Li, Feifei 1 ; Wu, Jingjing 1 ; Yue, Xiyan 1 ; Suo, Yujuan 2 ; Li, Jinliang 3 ; Wu, Fanhong 1 ; Yu, Yanyan 1 ;
作者机构： 1.Shanghai Inst Technol, Sch Chem & Environm Engn, Shanghai 201418, Peoples R China
2.Shanghai Acad Agr Sci, Inst Agrofood Stand & Testing Technol, Shanghai, Peoples R China
3.Aurisco Pharmaceut Co Ltd, Shanghai, Peoples R China
关键词： Berberine; alkyl ketone; C-8 substitution; antibacterial activity; foodborne pathogens
期刊名称：FOOD QUALITY AND SAFETY （ 影响因子：4.4； 五年影响因子：4.8 ）
ISSN： 2399-1399
年卷期： 2024 年 8 卷
页码：
收录情况： SCI
摘要： Natural berberine (BBR) exhibits good antimicrobial efficacy; however, its limited bioavailability greatly hinders its clinical application.The aim of this study is to synthesize a series of novel lipophilic C-8 substituted BBR prodrugs, conduct in vitro antibacterial activity tests on four common clinical pathogens, and further investigate their inhibitory mechanisms through bacterial membrane formation ability, cell permeability, hydrophobicity, and self-cohesion. Compound 14 showed the best activity with minimum inhibitory concentration (MIC) of 15.62 mu g/mL and minimum bactericidal concentration (MBC) of 31.25 mu g/mL against Staphylococcus aureus (ATCC 29213) and Listeria monocytogenes (4b G). In the mechanism study, compound 14 significantly inhibited bacterial biofilm formation by over 60% at a concentration of 0.5 MIC and enhanced cell membrane permeability by 40%. Meanwhile, compound 14 can interact with the cell membrane, exposing its hydrophobic regions and reducing the intercellular self-coagulation index to approximately 20%. The study indicates that the novel compound 14 enhanced the antibacterial efficacy by significantly reducing bacterial surface hydrophobicity and self-cohesion, as well as disrupting bacterial biofilm. In summary, we have created a series of 8-ketoberberine derivatives, which opens new prospects for BBR derivatives in the treatment of bacterial infections.
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