Benzenesulfonamide analogs of fluoroquinolones. Antibacterial Activity And QSAR Studies

NIETO, MARCELO J; ALOVERO FABIANA L.; MANZO RUBEN H; MAZZIERI, MARÍA ROSA

EUROPEAN JOURNAL OF MEDICAL CHEMISTRY

Elsevier

Lugar: Paris; Año: 2005 vol. 40 p. 361 - 369

0223-5234

The structure?activity relationships (SAR) of new antibacterial benzenesulfonamidefluoroquinolones (BSFQs), coming from derivatization piperazinyl of ciprofloxacin (CIP) were studied. The behavior of the new BSFQ series was similar to the previously norfloxacin (NOR) analogs reported, making possible a quantitative structure?activity relationships (QSAR) analysis of the complete set of BSFQs. The presence of the benzenesulfonylamido (BS) groups shifted the activity of classic antimicrobial fluoroquinolones from being more active against Gram-negative to Gram-positive strains. QSAR studies through Hansch analysis showed a linear correlation of the activity with electronic and steric parameters. Small electron-donor groups would increase the in vitro activity against Gram-positive bacteria. Hydrophobic properties played a minor role when activity is measured as minimum inhibitory concentration (MIC). QSAR analysis also reinforces previous biological findings about the presence of new interactions with target topoisomerases.