Antimicrobial activities of highly bioavailable organic salts and ionic liquids from fluoroquinolones

Santos, Miguel M.; Alves, Celso; Silva, Joana; Florindo, Catarina; Petrovski, Zeljko; Marrucho, Isabel M.; Pedrosa, Rui; Branco, Luís C.

http://hdl.handle.net/10400.8/5116

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Authors

Alves, Celso

Abstract(s)

As the development of novel antibiotics has been at a halt for several decades, chemically enhancing existing drugs is a very promising approach to drug development. Herein, we report the preparation of twelve organic salts and ionic liquids (OSILs) from ciprofloxacin and norfloxacin as anions with enhanced antimicrobial activity. Each one of the fluoroquinolones (FQs) was combined with six di erent organic hydroxide cations in 93–100% yield through a bu er-assisted neutralization methodology. Six of those were isomorphous salts while the remaining six were ionic liquids, with four of them being room temperature ionic liquids. The prepared compounds were not toxic to healthy cell lines and displayed between 47- and 1416-fold more solubility in water at 25 and 37 C than the original drugs, with the exception of the ones containing the cetylpyridinium cation. In general, the antimicrobial activity against Klebsiella pneumoniae was particularly enhanced for the ciprofloxacin-based OSILs, with up to ca. 20-fold decreases of the inhibitory concentrations in relation to the parent drug, while activity against Staphylococcus aureus and the commensal Bacillus subtilis strain was often reduced. Depending on the cation–drug combination, broad-spectrum or strain-specific antibiotic salts were achieved, potentially leading to the future development of highly bioavailable and safe antimicrobial ionic formulations.

Description

Funding: This work was supported by the Associate Laboratory for Green Chemistry LAQV and Centro de Química Estrutural, which are financed by national funds from FCT/MCTES (UIDB/50006/2020 and UID/QUI/00100/2013, respectively). The authors also thank Fundação para a Ciência e Tecnologia for the projects PTDC/QUI-OR/32406/2017, PEst-C/LA0006/2013, and ECI/BBBBQB/0230/2012, as well as one contract under Investigador FCT (L. C. Branco).

Keywords

Active pharmaceutical ingredients as organic salts and ionic liquids (API–OSILs) Antibiotics Ciprofloxacin Fluoroquinolones Ionic liquids Norfloxacin Polymorphism

URI

http://hdl.handle.net/10400.8/5116

Citation

Santos, M.M.; Alves, C.; Silva, J.; Florindo, C.; Costa, A.; Petrovski, Ž.; Marrucho, I.M.; Pedrosa, R.; Branco, L.C. Antimicrobial Activities of Highly Bioavailable Organic Salts and Ionic Liquids from Fluoroquinolones. Pharmaceutics 2020, 12, 694. DOI:10.3390/pharmaceutics12080694