Antituberculosis agents IV: in vitro antimycobacterial activity and cytotoxicity of N-piperazinyl quinolone derivatives containing 2-thienyl and 2-furyl moiety.

摘要

A series of N-[2-(2-furyl)-2-oxoethyl], N-[2-(2-furyl)-2-oxyiminoethyl], N-[2-oxo-2-(2-thienyl)ethyl] and N-[2-oxyimino-2-(2-thienyl)ethyl] piperazinyl quinolones (1a-h; 2a-h) were evaluated for antituberculosis activity against M. tuberculosis H37Rv using the BACTEC 460 radiometric system and BACTEC 12B medium. Our results indicated that compounds 1a, 1e and 1g were efficient antimycobacterial agents showing MIC values ranging from 0.78 to 6.25 microg/ml. In general, ciprofloxacin derivatives were more active than norfloxacin derivatives and the oxime analogues were less active than corresponding ketones. Active compounds (1a, 1e and 1g) were also screened by serial dilution to assess toxicity to VERO cell line. The cytotoxicity of tested compounds indicated that compound 1a was the less toxic compound (IC50 > 62.5 microg/ml). This compound was tested for efficacy in vitro in TB-infected macrophage model (EC90 = 3.25 microg/ml).