| Autor: |
Jednačak, Tomislav, Mikulandra, Ivana, Kapustić, Monika, Kušec, Iva, Smokrović, Kristina, Hošnjak, Ema, Piantanida, Ivo, Košćak, Marta, Zangger, Klaus, Novak, Predrag |
| Přispěvatelé: |
Bregović, Nikola, Namjesnik, Danijel, Novak, Predrag, Parlov Vuković, Jelena |
| Jazyk: |
angličtina |
| Rok vydání: |
2022 |
| Předmět: |
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| Popis: |
Macrolides belong to the largest class of antibiotics and are clinically used for the treatment of upper and lower respiratory tract infections. They inhibit the synthesis of bacterial proteins by reversible binding to the ribosomal 23S RNA at the peptidyl transferase region, which blocks the exiting tunnel for newly synthesized peptides. Despite the fact that new antibiotics have recently been developed, some bacteria have acquired broad resistance, representing a global medical problem, which can only be resolved by the discovery of novel and more potent drugs. It has been reported that linking known macrolides to bioactive thiosemicarbazones resulted with new conjugates, the macrozones, efficient against multidrug resistant strains. On the other hand, some thiosemicarbazones and their metal complexes showed anti-infective, antitumor and anti- inflammatory activity. In this work, we structurally characterized several azithromycin- derived macrozones and their metal complexes. Furthermore, interactions between the macrozones showing excellent in vitro activity and the E. coli ribosome were studied by a combination of NMR methods and fluorescence measurements. Transferred nuclear Overhauser effect (trNOE), saturation transfer difference (STD) and WaterLogsy experiments provided a wealth of information about ligand conformations and binding epitopes. Fluorescence measurements revealed binding constants. The obtained results can serve as a good basis for the design and development of macrolide conjugates with enhanced biological properties. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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