Synthesis and antimycobacterial evaluation of various 7-substituted ciprofloxacin derivatives

Tuberculosis continues to be a major cause of morbidity and mortality all over the world. Various 7-substituted ciprofloxacin derivatives were synthesized and evaluated for antimycobacterial activity in vitro and in vivo against Mycobacterium tuberculosis and for inhibition of the supercoiling activity of DNA gyrase from Mycobacterium smegmatis. Preliminary results indicated that most of the compounds demonstrated better in vitro antimycobacterial activity against M. tuberculosis than ciprofloxacin. Compound 1-cyclopropyl-6-fluoro-1,4-dihydro-4-oxo-7-[[N4-[1′-(5-methylisatinyl-β-semicarbazo)]methyl]N1-piperazinyl]-3-quinoline carboxylic acid (3h) decreased the bacterial load in spleen tissue with 0.76-log10 protections and was considered to be moderately active in reducing bacterial count in spleen. The results demonstrated the potential and importance of developing new quinolone derivatives against mycobacterial infections.

Various 7-substituted ciprofloxacin derivatives were synthesized and evaluated for antimycobacterial in vitro and in vivo against Mycobacterium tuberculosis and tested the ability of representative compounds to inhibit the supercoiling activity of DNA gyrase from Mycobacterium smegmatis. Five compounds (3a, g–i, and k) showed most promising activity with MIC90 of 0.78 μg/mL and were more potent than parent compound ciprofloxacin. Compound 3h decreased the bacterial load in spleen tissue with 0.76-log10 protections and was considered to be moderately active in reducing bacterial count in spleen.Figure optionsDownload as PowerPoint slide