作为新型具有抗细菌生物膜活性的两亲性材料—鼠李糖苷的结构与活性之间的关系研究

doi:10.5246/jcps.2018.12.082

中国药学(英文版) ›› 2018, Vol. 27 ›› Issue (12): 817-823.DOI: 10.5246/jcps.2018.12.082

• 【研究论文】 • 下一篇

作为新型具有抗细菌生物膜活性的两亲性材料—鼠李糖苷的结构与活性之间的关系研究

彭光华¹, 张文茜¹, 宋茂远¹, 殷梦雅¹, 王佳星¹, 李佳佳¹, 刘雅婕¹, 张媛媛¹, 李馨儒^1*, 李桂玲^2*

1. 北京大学医学部药学院分子药剂学与新释药系统北京市重点实验室, 北京 100191
2. 中国医学科学院医药生物技术研究所制剂室, 北京 100050

收稿日期:2018-05-24 修回日期:2018-10-23 出版日期:2018-12-30 发布日期:2018-11-05
通讯作者: Tel.: +86-010-82805360, E-mail: ll@bjmu.edu.cn; liguiling99@gmail.com
基金资助:
National Natural Science Foundation of China (Grant No. 81573381), and CAMS Initiative for Innovative Medicine (Grant No. CAMS-I2M-1-012).

The relationship between structural parameters and antibacterial biofilm activity for alkyl rhamnoside as a novel amphiphilic material

Guanghua Peng¹, Wenxi Zhang¹, Maoyuan Song¹, Mengya Yin¹, Jiaxing Wang¹, Jiajia Li¹, Yajie Liu¹, Yuanyuan Zhang¹, Xinru Li^1*, Guiling Li^2*

1. Beijing Key Laboratory of Molecular Pharmaceutics and New Drug System; School of Pharmaceutical Sciences, Pekig University Health Science Center, Beijing 100191, China
2. Institute of Medicinal Biotechnology, Chinese Academy of Medical Science & Peking Union Medical College, Beijing 100050, China

Received:2018-05-24 Revised:2018-10-23 Online:2018-12-30 Published:2018-11-05
Contact: Tel.: +86-010-82805360, E-mail: ll@bjmu.edu.cn; liguiling99@gmail.com
Supported by:
National Natural Science Foundation of China (Grant No. 81573381), and CAMS Initiative for Innovative Medicine (Grant No. CAMS-I2M-1-012).

摘要/Abstract

摘要：

本研究的目的在于探究新型两亲性材料—鼠李糖苷抗细菌生物膜活性的构效关系, 为选择具有最佳抗细菌生物膜活性的鼠李糖苷提供依据。成功合成得到一系列具有不同碳链长度的烷基鼠李糖苷, 并用¹H NMR进行了结构表征, 用荧光探针法测定其临界胶束浓度(CMC), 计算得到其亲水亲油平衡值(HLB), 用肉汤二倍稀释法测定其抗金黄色葡萄球菌的最低抑菌浓度, 用结晶紫法测定生物膜抑制和生物膜拆分效应。研究结果表明, 随碳链长度的增加, 烷基鼠李糖苷的CMC和HLB呈直线下降趋势, 表明其疏水性和表面活性随之增强; 十二烷基鼠李糖苷具有最强的体外抗菌活性, 同时也具有最强的体外抗细菌生物膜活性。该研究结果预示, 通过构效关系可以获得具有最强抗细菌生物膜活性的鼠李糖苷材料。

关键词: 生物膜, 烷基鼠李糖苷, 两亲性材料, 构效关系

Abstract:

In the present study, we aimed to explore the structure-activity relationship for the new amphiphilic material rhamnoside with antibacterial biofilm activity, and provide the basis for selecting rhamnoside with the optimum antibacterial biofilm activity. A series of alkyl rhamnosides with different carbon chain lengths were obtained by a simple and effective synthesis method. The structure was characterized by ¹H NMR spectrum, and their critical micelle concentration (CMC) was measured by fluorescence probe method. The hydrophilic and lipophilic balance (HLB) value was obtained by calculation. The minimal inhibitory concentration (MIC) of Staphylococcus aureus was determined by the broth double dilution method. The effect of biofilm inhibition and biofilm disruption was assayed by crystal violet method. The results showed that with the increase of carbon chain length, the CMC and HLB of alkyl rhamnosides displayed a linear downward trend, indicating that the lipophilicity and surface activityof the alkyl rhamnoside were increased. At the same time, the antibacterial activity in vitro produced the maximum, ie, 12-hydroxydecanoyl rhamnoside had the strongest antibacterial activity in vitro. Similarly, this material also exhibited the strongest antibacterial biofilm activity in vitro. The results of this study demonstrated that the most potent active material was obtained through the structure-activity relationship and it could be applied antibacterial biofilms in clinical practice.

Key words: Biofilm, Alkyl rhamnoside, Amphiphilic material, Structure-activity relationship

中图分类号:

R943

Supporting:

彭光华, 张文茜, 宋茂远, 殷梦雅, 王佳星, 李佳佳, 刘雅婕, 张媛媛, 李馨儒, 李桂玲. 作为新型具有抗细菌生物膜活性的两亲性材料—鼠李糖苷的结构与活性之间的关系研究[J]. 中国药学(英文版), 2018, 27(12): 817-823.

Guanghua Peng, Wenxi Zhang, Maoyuan Song, Mengya Yin, Jiaxing Wang, Jiajia Li, Yajie Liu, Yuanyuan Zhang, Xinru Li, Guiling Li. The relationship between structural parameters and antibacterial biofilm activity for alkyl rhamnoside as a novel amphiphilic material[J]. Journal of Chinese Pharmaceutical Sciences, 2018, 27(12): 817-823.

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作为新型具有抗细菌生物膜活性的两亲性材料—鼠李糖苷的结构与活性之间的关系研究

The relationship between structural parameters and antibacterial biofilm activity for alkyl rhamnoside as a novel amphiphilic material

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