Synthesis of cephalosporin-3 '-diazeniumdiolates: biofilm dispersing NO-donor prodrugs activated by beta-lactamase

Use of biofilm dispersing NO-donor compounds in combination with antibiotics has emerged as a promising new strategy for treating drug-resistant bacterial biofilm infections. This paper details the synthesis and preliminary evaluation of six cephalosporin-3 '-diazeniumdiolates as biofilm-targeted NO-donor prodrugs. Each of the compounds is shown to selectively release NO following reaction with the bacteria-specific enzyme beta-lactamase and to trigger dispersion of Pseudomonas aeruginosa biofilms in vitro.