Benzenesulfonamide analogs of fluoroquinolones. Antibacterial activity and QSAR studies.
The structure-activity relationships (SAR) of new antibacterial benzenesulfonamidefluoroquinolones (BSFQs), coming from derivatization of N4-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.
Nieto
M J
MJ
Departamento de Farmacia, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Ciudad Universitaria, 5000 Córdoba, Argentina. mnieto@olemiss.edu
Alovero
F L
FL
Manzo
R H
RH
Mazzieri
Maria R
MR
D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D001419:Bacteria / Q000187:drug effects; D024841:Fluoroquinolones / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D057927:Hydrophobic and Hydrophilic Interactions; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D021281:Quantitative Structure-Activity Relationship; D013449:Sulfonamides / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D000096926:Benzenesulfonamides
D000900:Anti-Bacterial Agents; D024841:Fluoroquinolones; D013449:Sulfonamides; D000096926:Benzenesulfonamides