Synthesis and Antimycobacterial Evaluation on Arylsulfonyl and Arylcarbonyl Derivatives of Ofloxacin

Four ofloxacin derivatives 3, 5, 6, and 11 were found to exhibit > 90% inhibition on the growth of M. tuberculosis at a concentration of 6.25 mu g/mL. Compounds 3, 5 and 11 have also exhibited a broad spectrum of antibacterial activities while 8-fluoro-3-methyl-9-[4-(4-nitrophenylsulfonyl)piperazin-1-yl)-6-oxo-2,3-dihydro-6H-1-oxo-3a-azaphenalene-5-carboxylic acid (6), which exhibited potent activity against the growth of TB with the MIC of 2.23 mu g/mL and a selectivity index (SI) of > 14.80, was inactive against the growth of G(+)- and G(-)-bacteria. Selective anti-TB activity was achieved by the introduction of an arylsulfonyl group at C-7 piperazin-4-yl of N-demethyl ofloxacin. Compound 6 is species-specific, exhibiting no significant activity against the growth of bacterial species other than M. tuberculosis, which implied the possibility of developing new specific anti-TB drug candidates without inducing cross resistance with other currently used antibacterial drugs. Structural optimization of 6 is on-going.