{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,13]],"date-time":"2026-01-13T21:32:54Z","timestamp":1768339974167,"version":"3.49.0"},"reference-count":52,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2020,7,23]],"date-time":"2020-07-23T00:00:00Z","timestamp":1595462400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>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 different organic hydroxide cations in 93\u2013100% yield through a buffer-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 \u00b0C 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\u2013drug combination, broad-spectrum or strain-specific antibiotic salts were achieved, potentially leading to the future development of highly bioavailable and safe antimicrobial ionic formulations.<\/jats:p>","DOI":"10.3390\/pharmaceutics12080694","type":"journal-article","created":{"date-parts":[[2020,7,23]],"date-time":"2020-07-23T11:26:01Z","timestamp":1595503561000},"page":"694","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":40,"title":["Antimicrobial Activities of Highly Bioavailable Organic Salts and Ionic Liquids from Fluoroquinolones"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8973-1595","authenticated-orcid":false,"given":"Miguel M.","family":"Santos","sequence":"first","affiliation":[{"name":"LAQV-REQUIMTE, Departamento de Qu\u00edmica, Faculdade de Ci\u00eancias e Tecnologia, Universidade Nova de Lisboa, 2829-516 Caparica, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1581-2127","authenticated-orcid":false,"given":"Celso","family":"Alves","sequence":"additional","affiliation":[{"name":"MARE\u2013Marine and Environmental Sciences Centre, ESTM, Instituto Polit\u00e9cnico de Leiria, 2520-641 Peniche, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1224-1699","authenticated-orcid":false,"given":"Joana","family":"Silva","sequence":"additional","affiliation":[{"name":"MARE\u2013Marine and Environmental Sciences Centre, ESTM, Instituto Polit\u00e9cnico de Leiria, 2520-641 Peniche, Portugal"}]},{"given":"Catarina","family":"Florindo","sequence":"additional","affiliation":[{"name":"Centro de Qu\u00edmica Estrutural, Instituto Superior T\u00e9cnico, Universidade de Lisboa, Avenida Rovisco Pais, 1049-001 Lisboa, Portugal"}]},{"given":"Alexandra","family":"Costa","sequence":"additional","affiliation":[{"name":"LAQV-REQUIMTE, Departamento de Qu\u00edmica, Faculdade de Ci\u00eancias e Tecnologia, Universidade Nova de Lisboa, 2829-516 Caparica, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8104-7008","authenticated-orcid":false,"given":"\u017deljko","family":"Petrovski","sequence":"additional","affiliation":[{"name":"LAQV-REQUIMTE, Departamento de Qu\u00edmica, Faculdade de Ci\u00eancias e Tecnologia, Universidade Nova de Lisboa, 2829-516 Caparica, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8733-1958","authenticated-orcid":false,"given":"Isabel M.","family":"Marrucho","sequence":"additional","affiliation":[{"name":"Centro de Qu\u00edmica Estrutural, Instituto Superior T\u00e9cnico, Universidade de Lisboa, Avenida Rovisco Pais, 1049-001 Lisboa, Portugal"}]},{"given":"Rui","family":"Pedrosa","sequence":"additional","affiliation":[{"name":"MARE\u2013Marine and Environmental Sciences Centre, ESTM, Instituto Polit\u00e9cnico de Leiria, 2520-641 Peniche, Portugal"}]},{"given":"Lu\u00eds C.","family":"Branco","sequence":"additional","affiliation":[{"name":"LAQV-REQUIMTE, Departamento de Qu\u00edmica, Faculdade de Ci\u00eancias e Tecnologia, Universidade Nova de Lisboa, 2829-516 Caparica, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2020,7,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"482","DOI":"10.2165\/00003495-198530060-00003","article-title":"Norfloxacin. 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