title: Ring-substituted 8-hydroxyquinoline-2-carboxanilides as potential antimycobacterial agents.
abstract: 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.
authors.affiliation: Department of Chemical Drugs, Faculty of Pharmacy, University of Veterinary and Pharmaceutical Sciences, Palackeho 1/3, 612 42 Brno, Czech Republic.
authors.forename: Jiri
authors.initials: J
authors.lastname: Kos
authors.affiliation: Department of Chemical Drugs, Faculty of Pharmacy, University of Veterinary and Pharmaceutical Sciences, Palackeho 1/3, 612 42 Brno, Czech Republic.
authors.forename: Iveta
authors.initials: I
authors.lastname: Zadrazilova
authors.affiliation: Department of Biological Sciences, Cork Institute of Technology, Bishopstown, Cork, Ireland.
authors.forename: Eoghan
authors.initials: E
authors.lastname: Nevin
authors.affiliation: 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.
authors.forename: Michal
authors.initials: M
authors.lastname: Soral
authors.affiliation: Department of Chemical Drugs, Faculty of Pharmacy, University of Veterinary and Pharmaceutical Sciences, Palackeho 1/3, 612 42 Brno, Czech Republic.
authors.forename: Tomas
authors.initials: T
authors.lastname: Gonec
authors.affiliation: Department of Human Pharmacology and Toxicology, Faculty of Pharmacy, University of Veterinary and Pharmaceutical Sciences, Palackeho 1/3, 612 42 Brno, Czech Republic.
authors.forename: Peter
authors.initials: P
authors.lastname: Kollar
authors.affiliation: Global Change Research Centre AS CR, Belidla 986/4a, 603 00 Brno, Czech Republic.
authors.forename: Michal
authors.initials: M
authors.lastname: Oravec
authors.affiliation: Department of Biological Sciences, Cork Institute of Technology, Bishopstown, Cork, Ireland.
authors.forename: Aidan
authors.initials: A
authors.lastname: Coffey
authors.affiliation: Department of Biological Sciences, Cork Institute of Technology, Bishopstown, Cork, Ireland.
authors.forename: Jim
authors.initials: J
authors.lastname: O'Mahony
authors.affiliation: 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.
authors.forename: Tibor
authors.initials: T
authors.lastname: Liptaj
authors.affiliation: Institute of Chemistry, Faculty of Natural Sciences, Comenius University, Mlynska dolina Ch-2, 842 15 Bratislava, Slovakia.
authors.forename: Katarina
authors.initials: K
authors.lastname: Kralova
authors.affiliation: 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.
authors.forename: Josef
authors.initials: J
authors.lastname: Jampilek
mesh_terms: D000900:Anti-Bacterial Agents / Q000737:chemistry* / Q000494:pharmacology*; D002460:Cell Line; D004353:Drug Evaluation, Preclinical / Q000379:methods; D006801:Humans; D008826:Microbial Sensitivity Tests; D009162:Mycobacterium avium / Q000187:drug effects; D009169:Mycobacterium tuberculosis / Q000187:drug effects / Q000378:metabolism; D015125:Oxyquinoline / Q000737:chemistry; D013329:Structure-Activity Relationship; D018675:Toxicity Tests
chemical_list: D000900:Anti-Bacterial Agents; D015125:Oxyquinoline
keywords: 8-Hydroxyquinolines; In vitro antimycobacterial activity; In vitro cytotoxicity; MTT assay; Structure–activity relationships