New fluorine-containing hydrazones active against MDR-tuberculosis
Language English Country France Media print-electronic
Document type Journal Article, Research Support, Non-U.S. Gov't
PubMed
21855181
DOI
10.1016/j.ejmech.2011.07.052
PII: S0223-5234(11)00565-4
Knihovny.cz E-resources
- MeSH
- Antitubercular Agents chemistry metabolism pharmacology MeSH
- Cell Line MeSH
- Fluorine chemistry metabolism pharmacology MeSH
- Hydrazones chemistry metabolism pharmacology MeSH
- Plasma metabolism MeSH
- Rats MeSH
- Humans MeSH
- Microbial Sensitivity Tests MeSH
- Tuberculosis, Multidrug-Resistant drug therapy MeSH
- Mycobacterium kansasii drug effects MeSH
- Mycobacterium drug effects MeSH
- Animals MeSH
- Check Tag
- Rats MeSH
- Humans MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- Antitubercular Agents MeSH
- Fluorine MeSH
- Hydrazones MeSH
Several new fluorine-containing hydrazones were synthesized and screened for their in vitro antimycobacterial activity. Nine of these derivatives have shown a remarkable activity against MDR-TB strain with MIC 0.5 μg/mL and high value of selectivity index (SI). Compound 3h with the highest SI (1268.58) was used for stability evaluation with putative metabolites (ciprofloxacin and formylciprofloxacin) detection. Compound 3h was stable at pH 7.4 of aqueous buffer and rat plasma, in acidic buffers (at pH 3 and 5) slow decomposition was observed. Interestingly, no formylciprofloxacin was detected in the solution, and only slightly increased concentration of ciprofloxacin was observed instead. Trifluoromethyl hydrazones 3f and 3g exhibited the best activity also against two strains of Mycobacterium kansasii (MIC 1-4 μmol/L). All evaluated compounds were found to be non-cytotoxic.
References provided by Crossref.org
N-substituted 2-isonicotinoylhydrazinecarboxamides--new antimycobacterial active molecules
