Synthesis and evaluation of biological activity for dual-acting antibiotics on the basis of azithromycin and glycopeptides.


Gause Institute of New Antibiotics, 11 B. Pirogovskaya, Moscow, Russia; D. Mendeleev University of Chemical Technology of Russia, 9 Miusskaya sq., Moscow, Russia. Electronic address: [Email]


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.


Antibacterial activity,Azithromycin,Dual action antibiotics,Eremomycin,Glycopeptide antibiotics,Macrolide antibiotics,Mechanism of action,Vancomycin,