RESUMO
OBJECTIVES AND METHODS: DRF 8417, a novel oxazolidinone, has been evaluated against Gram-positive and fastidious Gram-negative bacteria. In vitro activity of DRF 8417 was determined by broth microdilution method and in vivo efficacy studies were carried out in different murine systemic infection models. RESULTS: DRF 8417 exhibited potent activity against Gram-positive pathogens with MIC(50) and MIC(90) values ranging from 0.06 to 1 mg/L. MICs against Haemophilus influenzae and Moraxella catarrhalis were one to two dilutions lower than those of linezolid. The in vivo efficacy, by oral route, in different susceptible and resistant Gram-positive systemic bacterial infection models ranged from 2.0 to 2.9 mg/kg. CONCLUSIONS: These studies displayed the excellent in vitro and in vivo activity of DRF 8417 against Gram-positive pathogens and lower MICs when compared with linezolid against H. influenzae and M. catarrhalis.
Assuntos
Anti-Infecciosos , Infecções por Bactérias Gram-Negativas/tratamento farmacológico , Infecções por Bactérias Gram-Positivas/tratamento farmacológico , Cocos Gram-Positivos/efeitos dos fármacos , Haemophilus influenzae/efeitos dos fármacos , Moraxella catarrhalis/efeitos dos fármacos , Oxazolidinonas , Animais , Anti-Infecciosos/química , Anti-Infecciosos/farmacologia , Anti-Infecciosos/uso terapêutico , Modelos Animais de Doenças , Feminino , Infecções por Bactérias Gram-Negativas/microbiologia , Infecções por Bactérias Gram-Positivas/microbiologia , Infecções por Haemophilus/tratamento farmacológico , Infecções por Haemophilus/microbiologia , Haemophilus influenzae/enzimologia , Humanos , Masculino , Camundongos , Testes de Sensibilidade Microbiana , Infecções por Moraxellaceae/tratamento farmacológico , Infecções por Moraxellaceae/microbiologia , Oxazolidinonas/química , Oxazolidinonas/farmacologia , Oxazolidinonas/uso terapêutico , Organismos Livres de Patógenos Específicos , Resultado do Tratamento , Resistência beta-Lactâmica , beta-Lactamases/metabolismoRESUMO
With an intention to synergise the antibacterial activity of chalcones and oxazolidinones, several hybrid compounds possessing both chalcone and oxazolidinone moieties were synthesized and tested for antibacterial activity. The hybrid molecules containing heterocycles instead of aromatic ring were found to be active. A SAR study with various heterocycles resulted in a lead molecule 20, which was converted to one of the potent antibacterial compounds 27.
Assuntos
Antibacterianos/síntese química , Antibacterianos/farmacologia , Chalconas/síntese química , Chalconas/farmacologia , Oxazolidinonas/síntese química , Oxazolidinonas/farmacologia , Tiocarbamatos/síntese química , Tiocarbamatos/farmacologia , Antibacterianos/química , Chalconas/química , Testes de Sensibilidade Microbiana , Estrutura Molecular , Oxazolidinonas/química , Estereoisomerismo , Relação Estrutura-Atividade , Tiocarbamatos/químicaRESUMO
Some novel oxazolidinone derivatives with benzotriazole as pendant have been synthesized and tested for antibacterial activity. Linearly attached benzotriazole derivative showed more potency compared to angular one in vitro. Out of E/Z-isomers of angularly attached derivatives E-isomer was found to be more potent than Z-isomer. Either less active or inactive molecules were obtained, when benzotriazole was replaced with benzimidazole, benzthiazole, or benzoxazole. Finally, thioacetamide analogue of linear compound gave a lead having activity similar to linezolid in vitro.