RESUMEN
A series of novel 7-(3-aminopyrrolo[3,4-c]pyrazol-5(2H,4H,6H)-yl)-6-fluoro-4-oxo-1,4-dihydroquinoline-3-carboxylic acid derivatives was designed, synthesized and characterized by (1)H-NMR, MS and HRMS. These fluoroquinolones were evaluated for their in-vitro antibacterial activity against representative Gram-positive and Gram-negative strains. Generally, all of the target compounds display rather weak potency against the tested Gram-negative strains, but most of them exhibit good potency in inhibiting the growth of S. aureus including methicillin-resistant Staphylococcus aureus (MRSA) and Staphylococcus epidermidis including methicillin-resistant S. epidermidis (MRSE) (MIC: 0.125-8 µg/mL). In particular, the compound 9g is 2 to 32 fold more potent than gemifloxacin (GM), moxifloxacin (MX), gatifloxacin (GT), and levofloxacin (LV) against S. pneumoniae 08-3, K. pneumoniae 09-23, and P. aeruginosa ATCC27853, 4 to 32 fold more potent than MX, GM, and LV against K. pneumoniae 09-21, and more active than or comparable to the four reference drugs against P. aeruginosa 09-32.
Asunto(s)
Antibacterianos/síntesis química , Antibacterianos/farmacología , Fluoroquinolonas/síntesis química , Fluoroquinolonas/farmacología , Antibacterianos/análisis , Antibacterianos/química , Farmacorresistencia Bacteriana , Fluoroquinolonas/análisis , Fluoroquinolonas/química , Staphylococcus aureus Resistente a Meticilina/efectos de los fármacos , Pruebas de Sensibilidad Microbiana , Staphylococcus epidermidis/efectos de los fármacos , Relación Estructura-ActividadRESUMEN
A series of novel 7-[3-(N'-alkoxycarbamimidoyl)-4-(alkoxyimino)pyrrolidin-1-yl] fluoroquinolone derivatives were designed, synthesized and characterized by (1)H NMR, MS and HRMS. These fluoroquinolones were screened for their in vitro antibacterial activity. Most of them exhibit good potency in inhibiting the growth of Staphylococcus aureus and Staphylococcus epidermidis (MIC: 0.06-4.00 µg/mL). The activity of compounds 33 and 43 against S. aureus including MRSA and S. epidermidis including MRSE (MIC: 0.06-0.125 µg/mL) is more than or comparable to the reference drugs levofloxacin and gemifloxacin. In addition, compound 33 is 32 and 16-32 fold more potent than both the reference drugs against Enterococcus faecium 08-7 and Klebsiella pneumoniae 09-22, respectively.