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.

Sannio, F., Brizzi, A., Del Prete, R., Avigliano, M., Simone, T., Pagli, C., et al. (2022). Optimization of Pyrazole Compounds as Antibiotic Adjuvants Active against Colistin- and Carbapenem-Resistant Acinetobacter baumannii. ANTIBIOTICS, 11(12), 1-27 [10.3390/antibiotics11121832].

Optimization of Pyrazole Compounds as Antibiotic Adjuvants Active against Colistin- and Carbapenem-Resistant Acinetobacter baumannii

Sannio, Filomena;Brizzi, Antonella;Del Prete, Rosita;De Luca, Filomena;Paolino, Marco;Corelli, Federico;Mugnaini, Claudia;Docquier, Jean-Denis
2022-01-01

Abstract

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.
2022
Sannio, F., Brizzi, A., Del Prete, R., Avigliano, M., Simone, T., Pagli, C., et al. (2022). Optimization of Pyrazole Compounds as Antibiotic Adjuvants Active against Colistin- and Carbapenem-Resistant Acinetobacter baumannii. ANTIBIOTICS, 11(12), 1-27 [10.3390/antibiotics11121832].
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11365/1224494