Discovery of macrozones, new antimicrobial thiosemicarbazone-based azithromycin conjugates : design, synthesis and in vitro biological evaluation
Copyright © 2020 Elsevier Ltd and International Society of Antimicrobial Chemotherapy. All rights reserved..
Increasing bacterial resistance to existing antibiotics presents a serious threat to human health, and new antibacterial agents are desperately needed. Unfortunately, the number of newly marketed antibiotics has decreased dramatically in recent years. Withdrawal of the macrolide antibiotic telithromycin and the inability of solithromycin to gain marketing approval have prompted our efforts to search for new anti-infective macrolide compounds. Here we present the design, synthesis and biological evaluation of a novel hybrid class of azithromycin conjugates, the macrozones. Evaluation of prepared compounds against a panel of pathogenic bacteria revealed that these molecules showed excellent activities against susceptible Streptococcus pneumoniae, Streptococcus pyogenes and Enterococcus faecalis strains comparable with or better than azithromycin. Furthermore, prepared macrozones exhibited excellent activity against efflux resistant S. pneumoniae, which was 32 times better than that of azithromycin, and very good activity against an efflux resistant Staphylococcus aureus strain against which azithromycin is inactive. The results described here can serve as a good basis to guide further activities directed toward the discovery of more potent macrolide anti-infectives.
Medienart: |
E-Artikel |
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Erscheinungsjahr: |
2020 |
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Erschienen: |
2020 |
Enthalten in: |
Zur Gesamtaufnahme - volume:56 |
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Enthalten in: |
International journal of antimicrobial agents - 56(2020), 5 vom: 01. Nov., Seite 106147 |
Sprache: |
Englisch |
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Beteiligte Personen: |
Grgičević, Ivan [VerfasserIn] |
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Links: |
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Themen: |
83905-01-5 |
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Anmerkungen: |
Date Completed 06.07.2021 Date Revised 06.07.2021 published: Print-Electronic Citation Status MEDLINE |
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doi: |
10.1016/j.ijantimicag.2020.106147 |
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funding: |
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Förderinstitution / Projekttitel: |
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PPN (Katalog-ID): |
NLM314269193 |
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500 | |a published: Print-Electronic | ||
500 | |a Citation Status MEDLINE | ||
520 | |a Copyright © 2020 Elsevier Ltd and International Society of Antimicrobial Chemotherapy. All rights reserved. | ||
520 | |a Increasing bacterial resistance to existing antibiotics presents a serious threat to human health, and new antibacterial agents are desperately needed. Unfortunately, the number of newly marketed antibiotics has decreased dramatically in recent years. Withdrawal of the macrolide antibiotic telithromycin and the inability of solithromycin to gain marketing approval have prompted our efforts to search for new anti-infective macrolide compounds. Here we present the design, synthesis and biological evaluation of a novel hybrid class of azithromycin conjugates, the macrozones. Evaluation of prepared compounds against a panel of pathogenic bacteria revealed that these molecules showed excellent activities against susceptible Streptococcus pneumoniae, Streptococcus pyogenes and Enterococcus faecalis strains comparable with or better than azithromycin. Furthermore, prepared macrozones exhibited excellent activity against efflux resistant S. pneumoniae, which was 32 times better than that of azithromycin, and very good activity against an efflux resistant Staphylococcus aureus strain against which azithromycin is inactive. The results described here can serve as a good basis to guide further activities directed toward the discovery of more potent macrolide anti-infectives | ||
650 | 4 | |a Journal Article | |
650 | 4 | |a Antibacterials | |
650 | 4 | |a Azithromycin | |
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700 | 1 | |a Mikulandra, Ivana |e verfasserin |4 aut | |
700 | 1 | |a Bukvić, Mirjana |e verfasserin |4 aut | |
700 | 1 | |a Banjanac, Mihailo |e verfasserin |4 aut | |
700 | 1 | |a Radovanović, Vedrana |e verfasserin |4 aut | |
700 | 1 | |a Habinovec, Iva |e verfasserin |4 aut | |
700 | 1 | |a Bertoša, Branimir |e verfasserin |4 aut | |
700 | 1 | |a Novak, Predrag |e verfasserin |4 aut | |
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