The difluoroboranyl-norfloxacin complex “7a” induces an antimicrobial effect against K. pneumoniae strain in acute pneumonia murine model

Abstract

The discovery and implementation of antibiotics led to a better prognosis for infectious diseases. Fluoroquinolones are a family of antibiotics with a broad spectrum of action and antibacterial effectiveness. Because bacterial strains have increased their resistance to antibiotics, the World Health Organization has reported an urgent need to develop new active molecules. Our research group has therefore focused on deriving different compounds from fluoroquinolones. A fluoroquinolone derivatized in complex with boron, labeled 7a, was found to have good antibacterial potential. The objective of this research was to evaluate the in vitro and in vivo antimicrobial effect of the derivatized 7a on K. pneumoniae (clinical isolates) strains. The Kirby-Bauer inhibition technique generated average inhibition areas of 8.24 ± 1.239 cm2. For the minimum inhibitory concentration and minimum bactericidal concentration, macrodilutions of 7a compound were performed, obtaining 1 μg/mL in both determinations. For the in vivo model, Balb/c mice were infected intratracheally with K. pneumoniae; the animals were treated daily with ciprofloxacin (80 mg/kg/day) or 7a (80 mg/kg/day). The animals were sacrificed on the seventh day post-infection and hematoxylin and eosin staining was done on the lungs to evaluate the percentage of pneumonia. It was found that 7a significantly reduced the generation of pneumonia (5.96% of pneumonic tissue was found) while the untreated infected group generated 71.70% of pneumonic lung tissue. Compound 7a is an antimicrobial agent capable of inhibiting in vitro development of a Gram-negative (K. pneumoniae) bacterial strain. In addition, 7a is effective in treating acute pneumonia induced by K. pneumoniae in a murine model.

Keywords

• Fluoroquinolones
• Antimicrobial
• Docking
• Pneumonia
• Mice
• In vivo