RESUMO
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 ß-lactamase and to trigger dispersion of Pseudomonas aeruginosa biofilms in vitro.
Assuntos
Antibacterianos/metabolismo , Compostos Azo/metabolismo , Cefalosporinas/metabolismo , Doadores de Óxido Nítrico/metabolismo , Pró-Fármacos/metabolismo , beta-Lactamases/metabolismo , Antibacterianos/química , Compostos Azo/química , Biofilmes , Cefalosporinas/química , Doadores de Óxido Nítrico/química , Pró-Fármacos/química , Pseudomonas aeruginosa/fisiologiaRESUMO
Just say NO to biofilms: NO-donors are used to disperse a bacterial biofilm so that co-administered antibiotics will kill the more susceptible unattached cells. The chemically stable cephalosporin-3'-diazeniumdiolate NO-donor prodrug is activated by bacterial ß-lactamases and facilitates this two-step biofilm erradication.
Assuntos
Biofilmes/efeitos dos fármacos , Cefalosporinas/química , Pró-Fármacos/química , Pseudomonas aeruginosa/fisiologia , Antibacterianos/farmacologia , Doadores de Óxido Nítrico/química , Doadores de Óxido Nítrico/farmacologia , Pró-Fármacos/farmacologia , beta-Lactamases/metabolismoRESUMO
Remarkably high and regular enantioselectivities are obtained in Friedel-Crafts alkylation reactions involving alpha'-hydroxy enone templates and Cu(II)-bis(oxazoline) complexes as catalysts. The simple elaboration of adducts provides a route to enantioenriched aldehydes, carboxylic acids, and ketones containing the pyrrole and indole frameworks.
