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[摘要]：Novel 3'-piperazinyl derivatives of the 8-hydrogeno and 8-methoxy-6-fluoro-1-cyclopropyl-4quinolone-3-carboxylic acid scaffolds were designed, synthesized and characterized by H-1, C-13 and F-19 NMR, and HRMS. The activity of these derivatives against pathogenic mycobacteria (M. leprae and M. tuberculosis), wild-type (WT) strains or strains harboring mutations implicated in quinolone resistance, were determined by measuring drug concentrations inhibiting cell growth (MIC) and/or DNA supercoiling by DNA gyrase (IC50), or inducing 25% DNA cleavage by DNA gyrase (CC25). Compound 4 (with a methoxy in R-8 and a secondary carbamate in R-3') and compound 5 (with a hydrogen in R-8 and an ethyl ester in R-3') displayed biological activities close to those of ofloxacin but inferior to those of gatifloxacin and moxifloxacin against M. tuberculosis and M. leprae WT DNA gyrases, whereas all of the compounds were less active in inhibiting M. tuberculosis growth and M. leprae mutant DNA gyrases. Since R-3' substitutions have been poorly investigated previously, our results may help to design new quinolone derivatives in the future. (C) 2012 Elsevier Ltd. All rights reserved. |
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