RESUMO
An effort to identify novel inhibitors of peptidoglycan synthesis with antibacterial activity resulted in the discovery of a series of biaryl urea-based antibacterial agents through isolation of a by-product from a mixture-based combinatorial library of semi-carbazones and subsequent parallel synthesis efforts. The compounds were shown to possess broad spectrum antibacterial activity against gram-positive drug resistant pathogens, and showed apparent specificity for disruption of the bacterial cell wall biosynthesis pathway.
Assuntos
Antibacterianos/síntese química , Antibacterianos/farmacologia , Bactérias/efeitos dos fármacos , Hidrazinas/síntese química , Hidrazinas/farmacologia , Ureia/análogos & derivados , Ureia/química , Ureia/farmacologia , Bactérias/crescimento & desenvolvimento , Bactérias/ultraestrutura , Parede Celular/efeitos dos fármacos , Fenômenos Químicos , Físico-Química , Cromatografia Líquida de Alta Pressão , Técnicas de Química Combinatória , Espectrometria de Massas , Testes de Sensibilidade MicrobianaRESUMO
This reports the synthesis and in vitro antimicrobial properties of a series of 2-thioether-linked quinolonyl-carbapenems. Although the title compounds exhibited broad spectrum activity, the MICs were generally higher than those observed for selected benchmark carbapenems, quinolonyl-penems, and quinolones. Enzyme assays suggested that the title compounds are potent inhibitors of penicillin binding proteins and inefficient inhibitors of bacterial DNA-gyrase. Uptake studies indicated that the new compounds are not substrates for the norA encoded quinolone efflux pump.
