SAR Analysis of New Dual Targeting Fluoroquinolones. Implications of the Benzenesulfonyl Group

NIETO, M. J.; PIERINI, A. B.; SINGH, N.; MCCURDY, C. R.; MANZO, R. H.; MAZZIERI, M. R.

BENTHAM SCIENCE PUBL LTD

Lugar: Oak Park; Año: 2012 vol. 8 p. 349 - 349

hen a benzenesulfonyl moiety (BS) was bound to the N-piperazinyl ring of antibacterial fluoroquinolones (AMFQs) norfloxacin (NOR) or ciprofloxacin (CIP), the resulting benzenesulfonyl-fluoroquinolone (BSFQs) analogs showed an improved in vitro activity against Gram-positive strains. A bioisosterical replacement of the sulfonyl group for a carbonyl group led to the benzenecarboxamide-fluoroquinolones (BCFQs) that showed a similar trend in the antibacterial activity and spectrum. The BSFQs and BCFQs are considered members of the “dual targeting” fluoroquinolones, targeting both DNA gyrase and topoisomerase IV. To disclose the real contribution of the BS/BC moiety in antistaphylococcal activity, a 3D-QSAR analysis that included calculation of theoretical molecular descriptors and pharmacophore generation was performed. Previous and present QSAR results have confirmed the positive influence on activity of small electron donating p-substituent on the BS or BC moiety. The generated