Novel 1-(2-{3-/4-[(alkoxycarbonyl)amino]phenyl}-2-hydroxyethyl)-4-(2-fluorophenyl)-piperazin-1-ium chlorides (alkoxy = methoxy to butoxy; 8a-h) have been designed and synthesized through multistep reactions as a part of on-going research programme focused on finding new antimycobacterials. Lipophilic properties of these compounds were estimated by RP-HPLC using methanol/water mobile phases with a various volume fraction of the organic modifier. The log kw values, which were extrapolated from intercepts of a linear relationship between the logarithm of a retention factor k (log k) and volume fraction of a mobile phase modifier (ϕM), varied from 2.113 (compound 8e) to 2.930 (compound 8h) and indicated relatively high lipophilicity of these salts. Electronic properties of the molecules 8a-h were investigated by evaluation of their UV/Vis spectra. In a next phase of the research, the compounds 8a-h were in vitro screened against M. tuberculosis CNCTC My 331/88 (identical with H37Rv and ATCC 2794), M. kansasii CNCTC My 235/80 (identical with ATCC 12478), a M. kansasii 6 509/96 clinical isolate, M. avium CNCTC My 330/80 (identical with ATCC 25291) and M. avium intracellulare ATCC 13950, respectively, as well as against M. kansasii CIT11/06, M. avium subsp. paratuberculosis CIT03 and M. avium hominissuis CIT10/08 clinical isolates using isoniazid, ethambutol, ofloxacin, ciprofloxacin or pyrazinamide as reference drugs. The tested compounds 8a-h were found to be the most promising against M. tuberculosis; a MIC = 8 μM was observed for the most effective 1-(2-{4-[(butoxycarbonyl)amino]phen-ylphenyl}-2-hydroxyethyl)-4-(2-fluorophenyl)piperazin-1-ium chloride (8h). In addition, all of them showed low (insignificant) in vitro toxicity against a human monocytic leukemia THP-1 cell line, as observed LD50 values > 30 μM indicated. The structure-antimycobacterial activity relationships of the analyzed 8a-h series are also discussed.

Clinic for Tuberculosis and Lung Diseases National Institute for Tuberculosis Lung Diseases and Thoracic Surgery Vyšné Hágy Vysoké Tatry SK 059 84 Slovakia

Department of Biological Sciences Cork Institute of Technology Bishopstown Cork T12 P928 UK

Department of Chemical Drugs Faculty of Pharmacy University of Veterinary and Pharmaceutical Sciences in Brno Palackého 1946 1 Brno CZ 612 42 Czech Republic

Department of Human Pharmacology and Toxicology University of Veterinary and Pharmaceutical Sciences in Brno Palackého 1946 1 Brno CZ 612 42 Slovakia

Department of Pharmaceutical Analysis and Nuclear Pharmacy Faculty of Pharmacy Comenius University in Bratislava Odbojárov 10 Bratislava SK 832 32 Slovakia

Department of Pharmaceutical Chemistry Faculty of Pharmacy Comenius University in Bratislava Odbojárov 10 Bratislava SK 832 32 Slovakia

Department of Public Health Faculty of Health Catholic University in Ružomberok Hrabovská cesta 1A Ružomberok SK 034 01 Slovakia

Laboratory for Mycobacterial Diagnostics and Tuberculosis Regional Institute of Public Health Partyzánské náměstí 7 Ostrava CZ 702 00 Czech Republic

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