One of the promising directions of the combined approach is the design of dual-acting antibiotics – heterodimeric structures on the basis of antimicrobial agents of different classes. In this study a novel series of azithromycin-glycopeptide conjugates were designed and synthesized. The structures of the obtained compounds were confirmed using NMR spectroscopy and mass spectrometry data including MS/MS analysis. All novel hybrid antibiotics were found to be either as active as azithromycin and vancomycin against Gram-positive bacterial strains or have superior activity in comparison with their parent antibiotics. One compound, eremomycin-azithromycin conjugate 16, demonstrated moderate activity against Enterococcus faecium and Enterococcus faecalis strains resistant to vancomycin, and equal to vancomycin’s activity for the treatment of mice with Staphylococcus aureus sepsis.

结合方法的有希望的方向之一是设计双作用抗生素-基于不同类别抗微生物剂的异二聚体结构。在这项研究中，设计并合成了一系列新的阿奇霉素-糖肽结合物。使用NMR光谱法和包括MS / MS分析的质谱数据确认了所获得的化合物的结构。发现所有新的杂合抗生素对革兰氏阳性细菌菌株的活性都与阿奇霉素和万古霉素一样，或者比它们的母体抗生素具有更好的活性。一种化合物，eremomycin-azithromycin缀合物16对粪肠球菌和粪肠球菌具有中等活性对万古霉素具有抗性的菌株，与万古霉素对金黄色葡萄球菌脓毒症小鼠的治疗活性相等。