The Derivative Difluoroboranyl-Fluoroquinolone "7a" Generates Effective Inhibition Against the S. aureus Strain in a Murine Model of Acute Pneumonia.

Abstract

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.