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Optimization of Pyrazole Compounds as Antibiotic Adjuvants Active against Colistin- and Carbapenem-Resistant Acinetobacter baumannii
The diffusion of antibiotic-resistant, Gram-negative, opportunistic pathogens, an increasingly important global public health issue, causes a significant socioeconomic burden. Acinetobacter baumannii isolates, despite causing a lower number of infections than Enterobacterales, often show multidrug-r...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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MDPI
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9774939/ https://www.ncbi.nlm.nih.gov/pubmed/36551489 http://dx.doi.org/10.3390/antibiotics11121832 |
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author | Sannio, Filomena Brizzi, Antonella Del Prete, Rosita Avigliano, Marialuce Simone, Tiziana Pagli, Carlotta Ferraro, Teresa De Luca, Filomena Paolino, Marco Corelli, Federico Mugnaini, Claudia Docquier, Jean-Denis |
author_facet | Sannio, Filomena Brizzi, Antonella Del Prete, Rosita Avigliano, Marialuce Simone, Tiziana Pagli, Carlotta Ferraro, Teresa De Luca, Filomena Paolino, Marco Corelli, Federico Mugnaini, Claudia Docquier, Jean-Denis |
author_sort | Sannio, Filomena |
collection | PubMed |
description | The diffusion of antibiotic-resistant, Gram-negative, opportunistic pathogens, an increasingly important global public health issue, causes a significant socioeconomic burden. Acinetobacter baumannii isolates, despite causing a lower number of infections than Enterobacterales, often show multidrug-resistant phenotypes. Carbapenem resistance is also rather common, prompting the WHO to include carbapenem-resistant A. baumannii as a “critical priority” for the discovery and development of new antibacterial agents. In a previous work, we identified several series of compounds showing either direct-acting or synergistic activity against relevant Gram-negative species, including A. baumannii. Among these, two pyrazole compounds, despite being devoid of any direct-acting activity, showed remarkable synergistic activity in the presence of a subinhibitory concentration of colistin on K. pneumoniae and A. baumannii and served as a starting point for the synthesis of new analogues. In this work, a new series of 47 pyrazole compounds was synthesized. Some compounds showed significant direct-acting antibacterial activity on Gram-positive organisms. Furthermore, an evaluation of their activity as potential antibiotic adjuvants allowed for the identification of two highly active compounds on MDR Acinetobacter baumannii, including colistin-resistant isolates. This work confirms the interest in pyrazole amides as a starting point for the optimization of synergistic antibacterial compounds active on antibiotic-resistant, Gram-negative pathogens. |
format | Online Article Text |
id | pubmed-9774939 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-97749392022-12-23 Optimization of Pyrazole Compounds as Antibiotic Adjuvants Active against Colistin- and Carbapenem-Resistant Acinetobacter baumannii Sannio, Filomena Brizzi, Antonella Del Prete, Rosita Avigliano, Marialuce Simone, Tiziana Pagli, Carlotta Ferraro, Teresa De Luca, Filomena Paolino, Marco Corelli, Federico Mugnaini, Claudia Docquier, Jean-Denis Antibiotics (Basel) Article The diffusion of antibiotic-resistant, Gram-negative, opportunistic pathogens, an increasingly important global public health issue, causes a significant socioeconomic burden. Acinetobacter baumannii isolates, despite causing a lower number of infections than Enterobacterales, often show multidrug-resistant phenotypes. Carbapenem resistance is also rather common, prompting the WHO to include carbapenem-resistant A. baumannii as a “critical priority” for the discovery and development of new antibacterial agents. In a previous work, we identified several series of compounds showing either direct-acting or synergistic activity against relevant Gram-negative species, including A. baumannii. Among these, two pyrazole compounds, despite being devoid of any direct-acting activity, showed remarkable synergistic activity in the presence of a subinhibitory concentration of colistin on K. pneumoniae and A. baumannii and served as a starting point for the synthesis of new analogues. In this work, a new series of 47 pyrazole compounds was synthesized. Some compounds showed significant direct-acting antibacterial activity on Gram-positive organisms. Furthermore, an evaluation of their activity as potential antibiotic adjuvants allowed for the identification of two highly active compounds on MDR Acinetobacter baumannii, including colistin-resistant isolates. This work confirms the interest in pyrazole amides as a starting point for the optimization of synergistic antibacterial compounds active on antibiotic-resistant, Gram-negative pathogens. MDPI 2022-12-16 /pmc/articles/PMC9774939/ /pubmed/36551489 http://dx.doi.org/10.3390/antibiotics11121832 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Sannio, Filomena Brizzi, Antonella Del Prete, Rosita Avigliano, Marialuce Simone, Tiziana Pagli, Carlotta Ferraro, Teresa De Luca, Filomena Paolino, Marco Corelli, Federico Mugnaini, Claudia Docquier, Jean-Denis Optimization of Pyrazole Compounds as Antibiotic Adjuvants Active against Colistin- and Carbapenem-Resistant Acinetobacter baumannii |
title | Optimization of Pyrazole Compounds as Antibiotic Adjuvants Active against Colistin- and Carbapenem-Resistant Acinetobacter baumannii |
title_full | Optimization of Pyrazole Compounds as Antibiotic Adjuvants Active against Colistin- and Carbapenem-Resistant Acinetobacter baumannii |
title_fullStr | Optimization of Pyrazole Compounds as Antibiotic Adjuvants Active against Colistin- and Carbapenem-Resistant Acinetobacter baumannii |
title_full_unstemmed | Optimization of Pyrazole Compounds as Antibiotic Adjuvants Active against Colistin- and Carbapenem-Resistant Acinetobacter baumannii |
title_short | Optimization of Pyrazole Compounds as Antibiotic Adjuvants Active against Colistin- and Carbapenem-Resistant Acinetobacter baumannii |
title_sort | optimization of pyrazole compounds as antibiotic adjuvants active against colistin- and carbapenem-resistant acinetobacter baumannii |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9774939/ https://www.ncbi.nlm.nih.gov/pubmed/36551489 http://dx.doi.org/10.3390/antibiotics11121832 |
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