Antituberculosis agents. III. In vitro evaluation of antimycobacterial activity and cytotoxicity of some N-piperazinyl quinolone derivatives.
A series of N-[2-oxo-2-(4-substitutedphenyl)ethyl]piperazinyl quinolones(1a-e,2a-e and 3a-c) and N-[2-hydroxyimino-2-(4-substitutedphenyl)ethyl]piperazinyl quinolones(1f-j,2f-j and 3d-f) were evaluated for antituberculosis activity against Mycobacterium tuberculosis H37R, using the BACTEC 460 radiometric system and BACTEC 12B medium. Active compounds were also screened by serial dilution to assess toxicity to a VERO cell line. Nine compounds were efficient antimycobacterial agents showing MIC values ranging from 0.78 to 6.25 micrograms/ml. Generally, ciprofloxacin derivatives were more active than norfloxacin and enoxacin derivatives and the oxime analogues were less active than corresponding ketones. The most selective and less toxic compound 1a was tested for efficacy in vitro in TB-infected macrophage model (EC90 = 3.68 micrograms/ml, EC99 = 9.18 micrograms/ml).
Department of Medicinal Chemistry, Faculty of Pharmacy, Kerman University of Medical Sciences, Kerman, Iran.
A
A
Foroumadi
F
F
Soltani
S
S
Emami
A
A
Davood
D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D000995:Antitubercular Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D002522:Chlorocebus aethiops; D006801:Humans; D066298:In Vitro Techniques; D008264:Macrophages / Q000187:drug effects / Q000382:microbiology; D008826:Microbial Sensitivity Tests; D009169:Mycobacterium tuberculosis / Q000187:drug effects; D011804:Quinolines / Q000138:chemical synthesis* / Q000494:pharmacology*; D014407:Tumor Cells, Cultured; D014709:Vero Cells
D000970:Antineoplastic Agents; D000995:Antitubercular Agents; D011804:Quinolines; C465499:n-piperazinylquinolone