文章基本信息

标题：THE SYNTHESIS AND IN VITRO SCREENING OF THE 2-/3--ALKOXYPHENYLCARBAMIC ACID DERIVATIVES CONTAINING A 4-(2-FLUOROPHENYL)PIPERAZIN-1-YL MOIETY AGAINST SOME NON-TUBERCULOUS MYCOBACTERIAL STRAINS
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作者：Ivan Malik ; Jana Curillova ; Jozef Csollei 等
期刊名称：Fresenius Environmental Bulletin
印刷版ISSN：1018-4619
出版年度：2017
卷号：26
期号：4
页码：2760-2771
语种：English
出版社：PSP Publishing
摘要：ABSTRAC The current research was focused on the synthesis of 2-/3-alkoxyphenylcarbamic acid derivatives 5a-5d containing a salt-forming 4"-(2"-fluoro-phenyl)piperazin-1 "-yl moiety and their in vitro antimycobacterial investigation. Chemical structures of prepared intermediates and final compounds, which were isolated as salts with hydrochloric acid, were confirmed by the IR, 1H NMR, and 13C NMR spectral data. In addition, the target molecules 5a-5d were characterized by the MS as well as elemental analyses readouts. The final salts were in vitro screened against Mycobacterium marinum CAMP 5644, M. kansasii DSM 44162, M. smegmatis ATCC 700084 and M. avium subsp. paratuberculosis CIT03, respectively. The isonia-zid, rifampicin and ciprofloxacin reference drugs were tested under the same experimental conditions as well. It was observed that both 3-alkoxy substituted derivatives 5c and 5d have shown the most promising potential against the M. kansasii strain with the MIC values of 145 ^mol-L1 (molecule 5c) and 70 (imol-L1 (5d), respectively. In the light of the structure-antimycobacterial activity relationships study, it was found that an alkoxy chain attached to the 3-position and its elongation (therefore, an increase in lipophilicity) were considered favorable structural and physicochemical requirements rather than the presence of the 2-alkoxy group. Those conclusions were consistent with the findings from previous in vitro screening of those compounds against another atypical mycobacterium, M. kansasii CNCTC My 235/80. The electronic, steric and lipohydrophilic properties of the substituent attached to a 4"--(substituted phenyl)piperazin-1"-yl fragment and its impact on the activity against given mycobacteria could be regarded as fairly comprehensive.