新型红霉素类大环内酯衍生物的合成及抗菌活性研究

目的对大环内酯类抗生素进行结构改造,拟筛选获得抗菌活性更高的候选药物;方法分别对氟红霉素和克拉霉素的C-3及C-ll,C-12进行结构修饰,设计合成了17个大环内酯类衍生物,采用微量稀释法测定了衍生物的最低抑菌浓度(MIC)。结果12d、12e和12f对B.sutilis 168和S.aMrei.USA300表现出了较好的抗菌活性;结论通过结构改造获得了抗菌活性增强的大环内酯类衍生物,进一步探讨了大环内酯类抗生素的构效关系,为后续研宄提供了参考。

Preparation and antimicrobial activity of the derivatives of erythromycin-based macrolides

Objective In order to screen the derivatives with higher antimicrobial activities through structural modification of erythromycin and clarithromycin. Methods Flurithromycin and clarithromycin were modified on the C-3, C-11, and C-12 positions, respectively, to obtain 17 macrolide derivatives. Then minimum inhibitory concentrations of these derivatives were tested using the mircodilution method. Results Among these derivatives, compounds 12d, 12e and 12f showed good antibacterial activity against both B. subtilis 168 and S. aureus USA 300. Conclusion Several macrolide derivatives with higher antimicrobial activities were obtained through structural modifications. Structure-activity relationships of macrolide antibiotics were further discussed, which provided a clue to design new macrolide