Novel fluorescent cephalosporins: Synthesis, antimicrobial activity and photodynamic inactivation of antibiotic resistant bacteria

Two novel fluorescent cephalosporins, TCA and TBCA, were synthesized and characterized by 1H NMR, 13C NMR, UV–vis, and fluorescence spectroscopies. Biological activity assays demonstrated that TCA inactivated a Klebsiella pneumonia strain that expressed extended-spectrum β-lactamases. Incubation of 6 μM TCA with K. pneumonia cultures resulted in cell death for 84% of the cells after 126 J/cm2 of light irradiation. In vitro, TCA exhibited a MIC = 0.5 μg/mL with Staphylococcus aureus. Kinetic evaluation revealed that TCA and TBCA were substrates for B1 and B3 subclass metallo-β-lactamases. TBCA exhibited stronger binding affinities to the Gram-positive bacterial strains MRSA1, MRSA2, and S. aureus with value of 2.95–6.59 μM per 108 cells/mL.

Photoinactivation of novel fluorescent cephalosporin TCA against K. pneumonia and fluorescence imaging of TBCA with Gram-positive bacterial strains MRSA2.Figure optionsDownload as PowerPoint slideHighlights
► Two novel fluorescent cephalosporins TCA and TBCA were designed and characterized.
► TCA exhibited photoinactivation of K. pneumonia & antimicrobial effect for S. aureus.
► TBCA could label Gram-positive bacterial strains MRSA1, MRSA2 and S. aureus.