title: Antituberculosis agents. VII. Synthesis and in vitro evaluation of antimycobacterial activity and cytotoxicity of some N-piperazinyl quinolone derivatives.
abstract: A series of N-[2-(2,4-dichlorophenyl)-2-oxoethyl] and N-[2-aryl-2-benzyloxyimino ethyl]piperazinyl quinolones (5-13) have been prepared as part of a study to examine the relationship between structural modification at 7-position and activity against Mycobacterium tuberculosis. Primary screening was conducted at concentration of 6.25 micrograms/ml against M. tuberculosis H37Rv using BACTEC 460 radiometric system and BACTEC 12B medium. The actual minimum inhibitory concentrations (MIC) were determined for compounds demonstrating at least 90% inhibition in the primary screening. The results demonstrate that substitution of phenyl ring with 4- fluoro, 2, 4-difluoro and 2,4-dichloro groups resulted in variable inhibition percentage (Inh% = 7-101). Despite the significant antituberculosis activity of ciprofloxacin and norfloxacin derivatives containing 2-(2,4-dichlorophenyl)-2-oxoethyl moiety (MIC = 0.39 & 6.25 micrograms/ml), compounds with 2-aryl-2-(hydroxyimino)ethyl, 2-aryl-2-(benzyloxyimino)ethyl and 2-aryl-2-(4-chlorobenzyloxyimino)ethyl did not show any activity (MIC > 6.25 micrograms/ml, Inh% = -7 to 75). Active compounds were also screened by serial dilution to assess toxicity to a VERO cell line. While the most active compound 5a was not soluble in tissue culture media, compound 5b showed IC50 = 5.3 micrograms/ml.
authors.affiliation: Department of Medicinal Chemistry, Faculty of Pharmacy, Kerman University of Medical Sciences, Kerman, Iran.
authors.forename: A
authors.initials: A
authors.lastname: Foroumadi
authors.forename: F
authors.initials: F
authors.lastname: Soltani
authors.forename: A
authors.initials: A
authors.lastname: Asadipour
mesh_terms: D000890:Anti-Infective Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D000995:Antitubercular Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D007202:Indicators and Reagents; D008826:Microbial Sensitivity Tests; D009169:Mycobacterium tuberculosis / Q000187:drug effects*; D010879:Piperazines / Q000138:chemical synthesis* / Q000494:pharmacology*; D015363:Quinolones / Q000138:chemical synthesis* / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D000890:Anti-Infective Agents; D000995:Antitubercular Agents; D007202:Indicators and Reagents; D010879:Piperazines; D015363:Quinolones