title: Synthesis and antimycobacterial properties of ring-substituted 6-hydroxynaphthalene-2-carboxanilides.
abstract: In this study, a series of twenty-two ring-substituted 6-hydroxynaphthalene-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. Derivatives substituted by trifluoromethyl, bromo, methyl and methoxy moieties in C'(3) and C'(4) positions of the anilide ring showed 2-fold higher activity against M. tuberculosis than isoniazid and 4.5-fold higher activity against M. avium subsp. paratuberculosis than rifampicin. 6-Hydroxy-N-(2-methylphenyl)naphthalene-2-carboxamide had MIC=29 μM against M. avium complex. A significant decrease of mycobacterial cell metabolism (viability of M. tuberculosis H37Ra) was observed using MTT assay. Screening of the cytotoxicity of the most effective antimycobacterial compounds was performed using the THP-1 cells, and no significant lethal effect was observed. 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 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 Human Pharmacology and Toxicology, Faculty of Pharmacy, University of Veterinary and Pharmaceutical Sciences, Palackeho 1/3, 612 42 Brno, Czech Republic.
authors.forename: Ivan
authors.initials: I
authors.lastname: Kushkevych
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 Chemical Drugs, Faculty of Pharmacy, University of Veterinary and Pharmaceutical Sciences, Palackeho 1/3, 612 42 Brno, Czech Republic.
authors.forename: Pavel
authors.initials: P
authors.lastname: Bobal
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: 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: D000813:Anilides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D006801:Humans; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D009161:Mycobacterium / Q000166:cytology / Q000187:drug effects*; D009284:Naphthols / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D000813:Anilides; D000900:Anti-Bacterial Agents; D009284:Naphthols
keywords: Hydroxynaphthalene-2-carboxanilides; In vitro antimycobacterial activity; In vitro cytotoxicity; MTT assay; Structure–activity relationships