Novel fluorescent cephalosporins: synthesis, antimicrobial activity and photodynamic inactivation of antibiotic resistant bacteria.
Xiao JM, Feng L, Zhou LS, Gao HZ, Zhang YL, Yang KW.
Two novel fluorescent cephalosporins, TCA and TBCA, were synthesized and characterized by (1)H NMR, (13)C 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/cm(2) 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 10(8) cells/mL.