RESUMEN
Herein we report a new library of 2,3-pyrrolidinedione analogues that expands on our previous report on the antimicrobial studies of this heterocyclic scaffold. The novel 2,3-pyrrolidinediones reported herein have been evaluated against S. aureus and methicillin-resistant S. aureus (MRSA) biofilms, and this work constitutes our first report on the antibiofilm properties of this class of compounds. The antibiofilm activity of these 2,3-pyrrolidinediones has been assessed through minimum biofilm eradication concentration (MBEC) and minimum biofilm inhibition concentration (MBIC) assays. The compounds displayed antibiofilm properties and represent intriguing scaffolds for further optimization and development.
Asunto(s)
Antibacterianos , Staphylococcus aureus Resistente a Meticilina , Antibacterianos/farmacología , Staphylococcus aureus , Resistencia a la Meticilina , Biopelículas , Pruebas de Sensibilidad MicrobianaRESUMEN
The failure of frontline antibiotics in the clinic is one of the most serious threats to human health and requires a multitude of novel therapeutics and innovative approaches to treatment so as to curtail the growing crisis. In addition to traditional resistance mechanisms resulting in the lack of efficacy of many antibiotics, most chronic and recurring infections are further made tolerant to antibiotic action by the presence of biofilms. Herein, we report an expanded set of 5-benzylidene-4-oxazolidinones that are able to inhibit the formation of Staphylococcus aureus biofilms, disperse preformed biofilms, and, in combination with common antibiotics, are able to significantly reduce the bacterial load in a robust collagen-matrix model of biofilm infection.
Asunto(s)
Antibacterianos/farmacología , Compuestos de Bencilideno/farmacología , Biopelículas/efectos de los fármacos , Oxazolidinonas/farmacología , Staphylococcus aureus/fisiología , Acinetobacter baumannii/efectos de los fármacos , Sinergismo Farmacológico , Staphylococcus aureus Resistente a Meticilina/efectos de los fármacos , Pruebas de Sensibilidad Microbiana , Relación Estructura-ActividadRESUMEN
Chloride, bromide and iodide are inhibitors of the copper-catalysed azide-alkyne cycloaddition, with iodide exhibiting the most detrimental effects on rates and yields. A study of this inhibition is presented, along with experimental protocols to accommodate the presence of halides in this widely used reaction.