engleski

Synthesis and characterization of macrozones, novel bioactive derivatives of azithromycin

Macrolides represent a group of antibiotics whose structure is characterized by a macrocyclic lactone ring linked to one or more sugars. Macrolides are bacteriostatic antibiotics, they bind to the 50S subunit of the bacterial ribosome and thus inhibit synthesis of proteins essential for the growth of bacteria. They are effective against Gram-positive and some Gram-negative bacteria. Azithromycin is a semi-synthetic derivative of erythromycin A and belongs to the group of azalides, 15-membered macrolide antibiotics. Azithromycin has excellent pharmacokinetic properties and demonstrates satisfactory biological activity. However, bacterial resistance has emerged due to the frequent use of drugs and there is a need to discover new, more effective antibiotics. As part of this study, macrozones (novel conjugates of azithromycin and thiosemicarbazone) were successfully prepared. Since thiosemicarbazones exhibit antitumor and antibacterial activity, they were used to chemically modify azithromycin at three different positions. Structure and biological activity of macrozones against susceptible and resistant bacterial strains were determined. They showed very good activities against susceptible S. pneumoniae, S. pyogenes and E. faecalis strains, and excellent activity against resistant S. pneumoniae and S. aureus strains. NMR spectroscopy was used to study interactions of prepared compounds with ribosome and to determine the binding epitopes.

azithromycin, interactions, macrolide antibiotics, macrozone, NMR spectroscopy, NOESY technique, ribosome, STD technique

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