During the last decades, most bacterial strains have become increasingly resistant to antibiotics. This led the WHO to declare a global emergency in 2017 and urge the development of new active compounds. Some families of antibiotics still show high antibacterial efficacy, as is the case of fluoroquinolones, which have a broad spectrum of action. For this reason, our research group derived several compounds from fluoroquinolones, selecting a compound with good antibacterial activity for further evaluations, a difluoroboranil-fluoroquinolone complex labeled 7a. Antibacterial activity was evaluated using the Kirby–Bauer method against S. aureus (clinical isolate HGZ2201#ID). The MIC and MBC were obtained by macrodilutions and reseeding. In vivo antimicrobial activity was evaluated in a Balb/c mouse model infected intratracheally with S. aureus and subsequently treated with ciprofloxacin or 7a (80 mg/kg/day) for five days. A mean of 8.55 ± 0.395 cm² inhibition area was observed using 7a, while ciprofloxacin generated a mean inhibition of 7.86 ± 0.231 cm². Compound 7a showed a MIC and MBC of 0.25 μg/mL. This reduced the generation of pneumonic lung tissue to 5.83%, while the untreated infected group generated 60.51% of pneumonic tissue. Compound 7a proved to be an antimicrobial agent capable of inhibiting the in vitro development of S. aureus. Furthermore, 7a showed effectiveness in decreasing the progression of acute pneumonia induced by S. aureus in a murine model.

Background: Cancer remains a leading cause of morbidity and mortality worldwide. According to the World Health Organization (WHO), lung cancer is the most prevalent type of cancer among both men and women. Despite the various pharmacological and biological treatments available for lung cancer, their effectiveness has often fallen short, and the side effects can be severe. Therefore, there is an ongoing need to identify and develop novel compounds with enhanced anti-tumor efficacy and improved safety profiles. Research has shown that fluoroquinolone derivatives exhibit a broad cytotoxic spectrum comparable to other drugs used in clinical chemotherapy. Objective: The aim of this work was to synthesize and evaluate the cytotoxic, anti-proliferative, and anti-tumor effects of FQB-1, a novel fluoroquinolone derivative. Results: In silico molecular docking analysis demonstrated a strong interaction between FQB-1 and human topoisomerase, with a binding affinity score of –9.8 kcal/mol. In vitro cytotoxicity and anti-proliferative assays were conducted using the Lewis Lung Carcinoma (LLC) cell line. FQB-1 was tested at concentrations of 2.5, 5.0, 25.0, 50.0, 100.0, and 150.0 µg/mL. Significant cytotoxic and anti-proliferative effects were observed at concentrations of 50–150 µg/mL after 24 h of treatment. To evaluate FQB-1′s efficacy in vivo, a syngeneic tumor model was established in C57BL/6 mice. Treatment with FQB-1 (100 mg/kg) resulted in a marked reduction in tumor volume compared to the untreated control group. Histopathological analysis of tumor tissues from treated animals revealed a decrease in mitotic index and an increase in necrotic regions, indicating compromised tumor viability. Conclusions: FQB-1 exhibits cytotoxic and anti-proliferative effects and can reduce tumor growth while compromising tumor viability.

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-α cells. Results: Compound 7a exhibited both MIC and MBC values of 0.25 μg/mL, while ciprofloxacin-resistant S. aureus strains did not exhibit a detectable MIC within the concentration range tested (up to 1024 μg/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.

La resistencia antimicrobiana representa una amenaza crítica para la salud pública mundial, comprometiendo la eficacia de antibióticos ampliamente utilizados como las fluoroquinolonas. Ante este escenario, el diseño racional de nuevos híbridos estructurales derivados de fluoroquinolonas ha emergido como una estrategia prometedora frente a patógenos multirresistentes, particularmente aquellos del grupo ESKAPE. En esta revisión se analizan estudios publicados entre 2019 a 2025 que integran metodologías in silico, principalmente acoplamiento molecular y predicciones ADMET, con evaluaciones in vitro de actividad antimicrobiana. Se comparan las energías de unión, interacciones clave y estabilidad de complejos proteína–ligando con valores experimentales de MIC, MBC y halos de inhibición para análogos de ciprofloxacino y norfloxacino. Los resultados evidencian una correlación positiva y consistente entre alta afinidad computacional y mayor potencia biológica en los híbridos más activos, especialmente aquellos dirigidos contra ADN girasa y topoisomerasa II/IV. Asimismo, se destacan casos donde predicciones in silico desfavorables anticiparon baja actividad experimental, confirmando su utilidad como filtros tempranos. No obstante, se identifican limitaciones asociadas a la permeabilidad celular, estabilidad química y mecanismos de acción alternativos, que pueden generar discrepancias entre ambos enfoques. En conjunto, la evidencia sugiere que la integración de análisis computacionales con validación microbiológica constituye una herramienta robusta y eficiente para optimizar el diseño de nuevos híbridos de fluoroquinolonas, acelerando la identificación de candidatos con potencial terapéutico frente a patógenos resistentes.