title: New fluorine-containing hydrazones active against MDR-tuberculosis.
abstract: 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.
authors.affiliation: Charles University, Faculty of Pharmacy, Department of Inorganic and Organic Chemistry, Heyrovského 1203, 500 05 Hradec Králové, Czech Republic.
authors.forename: Eva
authors.initials: E
authors.lastname: Vavříková
authors.forename: Slovenko
authors.initials: S
authors.lastname: Polanc
authors.forename: Marijan
authors.initials: M
authors.lastname: Kočevar
authors.forename: Kata
authors.initials: K
authors.lastname: Horváti
authors.forename: Szilvia
authors.initials: S
authors.lastname: Bosze
authors.forename: Jiřina
authors.initials: J
authors.lastname: Stolaříková
authors.forename: Kateřina
authors.initials: K
authors.lastname: Vávrová
authors.forename: Jarmila
authors.initials: J
authors.lastname: Vinšová
mesh_terms: D000818:Animals; D000995:Antitubercular Agents / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D002460:Cell Line; D005461:Fluorine / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D006801:Humans; D006835:Hydrazones / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D008826:Microbial Sensitivity Tests; D009161:Mycobacterium / Q000187:drug effects*; D019909:Mycobacterium kansasii / Q000187:drug effects; D010949:Plasma / Q000378:metabolism; D051381:Rats; D018088:Tuberculosis, Multidrug-Resistant / Q000188:drug therapy*
chemical_list: D000995:Antitubercular Agents; D006835:Hydrazones; D005461:Fluorine