银杏酸C17:1衍生物增效达托霉素抗粪肠球菌的发现与机制的初步研究

目的 发现有抗菌活性或是增效活性的银杏酸C17:1衍生物。方法 以银杏酸C17:1为底物，利用一些基团取代苯环上的羧基从而获得银杏酸C17:1衍生物，棋盘法设计试验，测定银杏酸C17:1及其衍生物联合抗生素的增效作用，通过测定Zeta电位、ROS、NPN吸收来探究增效机制。结果 银杏酸C17:1衍生物Ⅱ与达托霉素联合抗粪肠球菌的部分抑菌浓度指数(FICIs)为0.125~0.25，具有明显的协同效应，不仅能产生较高的活性氧，而且能在一定程度改变细胞膜的通透性。结论 银杏酸衍生物Ⅱ对达托霉素体外抗耐药株具有较好的增效作用，可能和ROS的激增以及膜通透性的改变有关。

The preliminary study on the discovery and mechanism of ginkgolic acid C17:1 derivatives synergistic with daptomycin against Enterococcus faecalis

Objective To discover ginkgolic acid C17:1 derivatives which have antibacterial or synergistic activity. Methods Ginkgolic acid C17:1 derivatives were obtained by substituting some groups for the carboxyl groups on the benzene rings. Their antibiotic-enhancing effects were determined on 96-well plate using checkerboard design. The synergistic mechanism was explored by measuring Zeta Potential, ROS and NPN absorption. Results The fractional inhibitory concentration indices (FICIs) of ginkgolic acid C17:1Ⅱ combined with daptomycin against Enterococcus faecalis were 0.125~0.25, a significant datum to prove the synergetic effect. Ginkgolic acid C17:1Ⅱ could not only produce higher reactive oxygen, but also changed the permeability of cell membrane to some extent. Conclusion Ginkgolic acid C17:1Ⅱ combined with daptomycin had good synergistic effect, which might be related to the proliferation of ROS and changes in membrane