Enhanced Antibacterial Activity of a Cationic Macromolecule by Its Complexation with a Weakly Active Pyrazole Derivative

Description

Molecules containing the pyrazole nucleus are widely reported as promising candidates to develop new antimicrobial compounds against multidrug‐resistant (MDR) bacteria, where available antibiotics may fail. Recently, aiming at improving the too‐high minimum inhibitory concentrations (MICs) of a pyrazole hydrochloride salt (CB1H), CB1H‐loaded nanoparticles (CB1H‐ P7 NPs) were developed using a potent cationic bactericidal macromolecule (P7) as polymer matrix. Here, CB1H‐P7 NPs have been successfully tested on several clinical isolates of Gram‐positive and Gram‐negative species, including relevant MDR strains. CB1H‐P7 NPs displayed very low MICs (0.6–4.8 μM), often two‐fold lower than those of P7, on 34 out of 36 isolates tested. Upon complexation, the antibacterial effects of pristine CB1H were improved by 2–16.4‐fold, and, unexpectedly, also the already potent antibacterial effects of P7 were 2–8 times improved against most of bacteria tested when complexed with CB1H. Time‐killing experiments performed on selected species established that CB1H‐P7 NPs were bactericidal against Staphylococcus aureus, Escherichia coli and Pseudomonas aeruginosa. Selectivity indices values up to 2.4, determined by cytotoxicity experiments on human keratinocytes, suggested that CB1H‐P7 NPs could be promising for counteracting serious infections sustained by most of the isolates tested in this study

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