In this study, a series of twenty-two ring-substituted 8-hydroxyquinoline-2-carboxanilides was prepared and characterized. Primary in vitro screening of the synthesized compounds was performed against Mycobacterium tuberculosis H37Ra, Mycobacterium avium complex and M. avium subsp. paratuberculosis. Some of the tested compounds showed the antimycobacterial activity against M. avium subsp. paratuberculosis comparable with or higher than that of rifampicin. 8-Hydroxy-N-[3-(trifluoromethyl)phenyl]- and 8-hydroxy-N-[4-(trifluoromethyl)phenyl]quinoline-2-carboxamide showed MIC=24 μM against all tested mycobacterial strains. 3-Methoxyphenyl- and 3-methylphenyl derivatives expressed MIC=27 or 29 μM also against all the tested strains. Their activity against M. avium subsp. paratuberculosis was 4-fold higher than that of rifampicin. 2-Bromophenyl- and 2-(trifluoromethyl)phenyl derivatives had MIC=23 or 24 μM against M. tuberculosis. A significant decrease of mycobacterial cell metabolism (viability of M. tuberculosis H37Ra) was observed using MTT assay. Screening of cytotoxicity of the compounds was performed using the THP-1 cells, and no significant lethal effect was observed up to tested concentration 30 μM. The structure-activity relationships are discussed.

Department of Biological Sciences Cork Institute of Technology Bishopstown Cork Ireland

Department of Chemical Drugs Faculty of Pharmacy University of Veterinary and Pharmaceutical Sciences Palackeho 1 3 612 42 Brno Czech Republic

Department of Human Pharmacology and Toxicology Faculty of Pharmacy University of Veterinary and Pharmaceutical Sciences Palackeho 1 3 612 42 Brno Czech Republic

Department of NMR Spectroscopy and Mass Spectrometry Faculty of Chemical and Food Technology Slovak University of Technology in Bratislava Radlinskeho 9 812 37 Bratislava Slovakia

Global Change Research Centre AS CR Belidla 986 4a 603 00 Brno Czech Republic

Institute of Chemistry Faculty of Natural Sciences Comenius University Mlynska dolina Ch 2 842 15 Bratislava Slovakia

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$a Ring-substituted 8-hydroxyquinoline-2-carboxanilides as potential antimycobacterial agents / $c J. Kos, I. Zadrazilova, E. Nevin, M. Soral, T. Gonec, P. Kollar, M. Oravec, A. Coffey, J. O'Mahony, T. Liptaj, K. Kralova, J. Jampilek,

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$a In this study, a series of twenty-two ring-substituted 8-hydroxyquinoline-2-carboxanilides was prepared and characterized. Primary in vitro screening of the synthesized compounds was performed against Mycobacterium tuberculosis H37Ra, Mycobacterium avium complex and M. avium subsp. paratuberculosis. Some of the tested compounds showed the antimycobacterial activity against M. avium subsp. paratuberculosis comparable with or higher than that of rifampicin. 8-Hydroxy-N-[3-(trifluoromethyl)phenyl]- and 8-hydroxy-N-[4-(trifluoromethyl)phenyl]quinoline-2-carboxamide showed MIC=24 μM against all tested mycobacterial strains. 3-Methoxyphenyl- and 3-methylphenyl derivatives expressed MIC=27 or 29 μM also against all the tested strains. Their activity against M. avium subsp. paratuberculosis was 4-fold higher than that of rifampicin. 2-Bromophenyl- and 2-(trifluoromethyl)phenyl derivatives had MIC=23 or 24 μM against M. tuberculosis. A significant decrease of mycobacterial cell metabolism (viability of M. tuberculosis H37Ra) was observed using MTT assay. Screening of cytotoxicity of the compounds was performed using the THP-1 cells, and no significant lethal effect was observed up to tested concentration 30 μM. The structure-activity relationships are discussed.

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$a Zadrazilova, Iveta $u Department of Chemical Drugs, Faculty of Pharmacy, University of Veterinary and Pharmaceutical Sciences, Palackeho 1/3, 612 42 Brno, Czech Republic.

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$a Nevin, Eoghan $u Department of Biological Sciences, Cork Institute of Technology, Bishopstown, Cork, Ireland.

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$a Soral, Michal $u Department of NMR Spectroscopy and Mass Spectrometry, Faculty of Chemical and Food Technology, Slovak University of Technology in Bratislava, Radlinskeho 9, 812 37 Bratislava, Slovakia.

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$a Gonec, Tomas $u Department of Chemical Drugs, Faculty of Pharmacy, University of Veterinary and Pharmaceutical Sciences, Palackeho 1/3, 612 42 Brno, Czech Republic.

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$a Kollar, Peter $u Department of Human Pharmacology and Toxicology, Faculty of Pharmacy, University of Veterinary and Pharmaceutical Sciences, Palackeho 1/3, 612 42 Brno, Czech Republic.

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$a Oravec, Michal $u Global Change Research Centre AS CR, Belidla 986/4a, 603 00 Brno, Czech Republic.

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$a Coffey, Aidan $u Department of Biological Sciences, Cork Institute of Technology, Bishopstown, Cork, Ireland.

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$a O'Mahony, Jim $u Department of Biological Sciences, Cork Institute of Technology, Bishopstown, Cork, Ireland.

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$a Liptaj, Tibor $u Department of NMR Spectroscopy and Mass Spectrometry, Faculty of Chemical and Food Technology, Slovak University of Technology in Bratislava, Radlinskeho 9, 812 37 Bratislava, Slovakia.

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$a Kralova, Katarina $u Institute of Chemistry, Faculty of Natural Sciences, Comenius University, Mlynska dolina Ch-2, 842 15 Bratislava, Slovakia.

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$a Jampilek, Josef $u Department of Chemical Drugs, Faculty of Pharmacy, University of Veterinary and Pharmaceutical Sciences, Palackeho 1/3, 612 42 Brno, Czech Republic. Electronic address: josef.jampilek@gmail.com.

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