New fluorine-containing hydrazones active against MDR-tuberculosis

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.

Graphical abstractFigure optionsDownload full-size imageDownload as PowerPoint slideHighlights► New fluorine-containing hydrazones with in vitro antimycobacterial activity were synthesized. ► Nine derivatives have shown activity against MDR-TB strain with MIC 0.5 mg/mL. ► The most active compound was stable at pH 7.4 of aqueous buffer and rat plasma. ► In acidic buffers slow decomposition of the most active compound was observed. ► All evaluated compounds were found to be non-cytotoxic.