N-Pyrazinylhydroxybenzamides as biologically active compounds : a hit-expansion study and antimicrobial evaluation
Background: The development of novel antimicrobial drugs is an essential part of combatting the uprising of antimicrobial resistance. Proper hit-to-lead development is crucially needed. Methods & results: We present a hit-expansion study of N-pyrazinyl- and N-pyridyl-hydroxybenzamides with a comprehensive determination of structure-activity relationships. The antimicrobial screening revealed high selectivity to staphylococci along with antimycobacterial activity with the best value of 6.25 μg/ml against Mycobacterium tuberculosis H37Rv. We proved an inhibition of proteosynthesis and a membrane depolarization of methicillin-resistant Staphylococcus aureus. Conclusion: Our results are a good starting point for further development of new antimicrobial compounds, where the next step would be tuning the potential between relatively nonspecific membrane depolarization effect and specific inhibition of proteosynthesis.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:15 |
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| Enthalten in: |
Future medicinal chemistry - 15(2023), 19 vom: 25. Okt., Seite 1791-1806 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Kerda, Marek [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 02.11.2023 Date Revised 13.11.2023 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.4155/fmc-2023-0189 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM363694838 |
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| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Background: The development of novel antimicrobial drugs is an essential part of combatting the uprising of antimicrobial resistance. Proper hit-to-lead development is crucially needed. Methods & results: We present a hit-expansion study of N-pyrazinyl- and N-pyridyl-hydroxybenzamides with a comprehensive determination of structure-activity relationships. The antimicrobial screening revealed high selectivity to staphylococci along with antimycobacterial activity with the best value of 6.25 μg/ml against Mycobacterium tuberculosis H37Rv. We proved an inhibition of proteosynthesis and a membrane depolarization of methicillin-resistant Staphylococcus aureus. Conclusion: Our results are a good starting point for further development of new antimicrobial compounds, where the next step would be tuning the potential between relatively nonspecific membrane depolarization effect and specific inhibition of proteosynthesis | ||
| 650 | 4 | |a Journal Article | |
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| 650 | 4 | |a antibacterial | |
| 650 | 4 | |a antimicrobial resistance | |
| 650 | 4 | |a antimycobacterial | |
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| 650 | 4 | |a macromolecular assay | |
| 650 | 4 | |a membrane depolarization | |
| 650 | 4 | |a minimum bactericidal concentration | |
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| 650 | 4 | |a water solubility | |
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| 700 | 1 | |a Šlechta, Petr |e verfasserin |4 aut | |
| 700 | 1 | |a Jand'ourek, Ondrej |e verfasserin |4 aut | |
| 700 | 1 | |a Konečná, Klara |e verfasserin |4 aut | |
| 700 | 1 | |a Hatoková, Paulina |e verfasserin |4 aut | |
| 700 | 1 | |a Paterová, Pavla |e verfasserin |4 aut | |
| 700 | 1 | |a Zitko, Jan |e verfasserin |4 aut | |
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