{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T11:49:25Z","timestamp":1788954565399,"version":"build-2803163510"},"reference-count":77,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2026,3,20]],"date-time":"2026-03-20T00:00:00Z","timestamp":1773964800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>According to the World Health Organization, antibiotic research remains insufficient, emphasizing the urgent need for new active molecules, particularly against resistant bacteria. Based on known antibacterial scaffolds, new fluoroquinolone derivatives have been synthesized by our research group, including compound 7a, a difluoroboranyl-fluoroquinolone that previously demonstrated activity against sensitive strains. Methods: The minimum inhibitory (MIC) and bactericidal (MBC) concentrations of compound 7a were determined against Staphylococcus aureus, Klebsiella pneumoniae, and Escherichia coli. The selective development of ciprofloxacin-resistant S. aureus was induced by reseeding the isolate on seven consecutive days with an antibiotic concentration that was not capable of inhibiting its development. Pharmacokinetic and toxicological properties were predicted using SwissADME, Way2Drug, and molecular docking (AutoDock Vina). In vivo toxicity was evaluated in BALB\/c mice through histopathological liver and kidney analysis and serum biochemical markers. The antibacterial efficacy of 7a (80 mg\/kg\/day) was assessed in a murine pneumonia model induced by ciprofloxacin-resistant S. aureus. DNA gyrase inhibition was confirmed through plasmid electrophoresis assays in E. coli DH5-\u03b1 cells. Results: Compound 7a exhibited both MIC and MBC values of 0.25 \u03bcg\/mL, while ciprofloxacin-resistant S. aureus strains did not exhibit a detectable MIC within the concentration range tested (up to 1024 \u03bcg\/mL). In silico predictions revealed favorable ADME profiles, low toxicity, and strong interaction with DNA gyrase. In vivo, 7a showed no signs of hepatotoxicity or nephrotoxicity and effectively reduced pneumonic tissue to 1.99% in infected mice. Electrophoretic assays confirmed DNA gyrase inhibition consistent with the mechanism of fluoroquinolones. Conclusions: Compound 7a evidenced activity against ciprofloxacin-resistant S. aureus in vitro and reduced infection progression in vivo. It also displays favorable drug-like properties, low predicted toxicity, and DNA gyrase inhibition.<\/jats:p>","DOI":"10.3390\/molecules31061044","type":"journal-article","created":{"date-parts":[[2026,3,20]],"date-time":"2026-03-20T17:02:43Z","timestamp":1774026163000},"page":"1044","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["The Difluoroboranyl-Fluoroquinolone Derivative \u201c7a\u201d Inhibits Bacterial DNA Gyrase and Exhibits Potent Activity Against Ciprofloxacin-Resistant S. aureus In Vitro and In Vivo Using an Acute Pneumonia Model"],"prefix":"10.3390","volume":"31","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0002-4419","authenticated-orcid":false,"given":"Luis Angel","family":"Veyna-Hurtado","sequence":"first","affiliation":[{"name":"Facultad de Ciencias Qu\u00edmicas, Universidad Aut\u00f3noma de San Luis Potos\u00ed, San Luis Potos\u00ed 78210, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4286-163X","authenticated-orcid":false,"given":"Hiram","family":"Hern\u00e1ndez-L\u00f3pez","sequence":"additional","affiliation":[{"name":"Laboratorio de Investigaci\u00f3n en S\u00edntesis Org\u00e1nica y Modificaci\u00f3n Qu\u00edmica, Unidad Acad\u00e9mica de Ciencias Qu\u00edmicas, Universidad Aut\u00f3noma de Zacatecas, Zacatecas 98160, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5291-2197","authenticated-orcid":false,"given":"Denisse","family":"de Loera","sequence":"additional","affiliation":[{"name":"Facultad de Ciencias Qu\u00edmicas, Universidad Aut\u00f3noma de San Luis Potos\u00ed, San Luis Potos\u00ed 78210, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan Manuel","family":"Vargas-Morales","sequence":"additional","affiliation":[{"name":"Laboratorio de An\u00e1lisis Cl\u00ednicos, Facultad de Ciencias Qu\u00edmicas, Universidad Aut\u00f3noma de San Luis Potos\u00ed, San Luis Potos\u00ed 78100, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1961-6919","authenticated-orcid":false,"given":"Mart\u00edn","family":"Mu\u00f1oz-Ortega","sequence":"additional","affiliation":[{"name":"Laboratorio de Patolog\u00eda Molecular, Departamento de Qu\u00edmica, Universidad Aut\u00f3noma de Aguascalientes, Aguascalientes 20100, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lorena","family":"Troncoso-V\u00e1zquez","sequence":"additional","affiliation":[{"name":"Departamento de Patolog\u00eda, Instituto Mexicano del Seguro Social (IMSS), Zacatecas 99000, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alondra","family":"Bocanegra-Zapata","sequence":"additional","affiliation":[{"name":"Facultad de Ciencias Qu\u00edmicas, Universidad Aut\u00f3noma de San Luis Potos\u00ed, San Luis Potos\u00ed 78210, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7344-353X","authenticated-orcid":false,"given":"Alberto Rafael","family":"Cervantes-Villagrana","sequence":"additional","affiliation":[{"name":"Laboratorio de Investigaci\u00f3n en Terap\u00e9utica Experimental, Unidad Acad\u00e9mica de Ciencias Qu\u00edmicas, Universidad Aut\u00f3noma de Zacatecas, Zacatecas 98160, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,3,20]]},"reference":[{"key":"ref_1","first-page":"237","article-title":"History of Antibiotics Research","volume":"398","author":"Mohr","year":"2016","journal-title":"Curr. 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