title: Synthesis and Biological Evaluation of N-Alkoxyphenyl-3-hydroxynaphthalene-2-carboxanilides.
abstract: A series of fifteen new N-alkoxyphenylanilides of 3-hydroxynaphthalene-2-carboxylic acid was prepared and characterized. Primary in vitro screening of the synthesized compounds was performed against Staphylococcus aureus, three methicillin-resistant S. aureus strains, Mycobacterium tuberculosis H37Ra and M. avium subsp. paratuberculosis. Some of the tested compounds showed antibacterial and antimycobacterial activity against the tested strains comparable with or higher than that of the standards ampicillin or rifampicin. 3-Hydroxy-N-(2-propoxyphenyl)naphthalene-2-carboxamide and N-[2-(but-2-yloxy)-phenyl]-3-hydroxynaphthalene-2-carboxamide had MIC = 12 µM against all methicillin-resistant S. aureus strains; thus their activity is 4-fold higher than that of ampicillin. The second mentioned compound as well as 3-hydroxy-N-[3-(prop-2-yloxy)phenyl]-naphthalene-2-carboxamide had MICs = 23 µM and 24 µM against M. tuberculosis respectively. N-[2-(But-2-yloxy)phenyl]-3-hydroxynaphthalene-2-carboxamide demonstrated higher activity against M. avium subsp. paratuberculosis than rifampicin. Screening of the cytotoxicity of the most effective antimycobacterial compounds was performed using THP-1 cells, and no significant lethal effect was observed for the most potent compounds. The compounds were additionally tested for their activity related to inhibition of photosynthetic electron transport (PET) in spinach (Spinacia oleracea L.) chloroplasts. N-(3-Ethoxyphenyl)-3-hydroxynaphthalene-2-carboxamide (IC50 = 4.5 µM) was the most active PET inhibitor. The structure-activity relationships are discussed.
authors.affiliation: Department of Chemical Drugs, Faculty of Pharmacy, University of Veterinary and Pharmaceutical Sciences, Palackeho 1/3, 61242 Brno, Czech Republic. t.gonec@seznam.cz.
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, 61242 Brno, Czech Republic. cizeka@vfu.cz.|Department of Infectious Diseases and Microbiology, Faculty of Veterinary Medicine, University of Veterinary and Pharmaceutical Sciences, Palackeho 1/3, 61242 Brno, Czech Republic. cizeka@vfu.cz.
authors.forename: Iveta
authors.initials: I
authors.lastname: Zadrazilova
authors.affiliation: Department of Biological Sciences, Cork Institute of Technology, Bishopstown, Cork, Ireland. eoghan.nevin@mycit.ie.
authors.forename: Eoghan
authors.initials: E
authors.lastname: Nevin
authors.affiliation: Department of Human Pharmacology and Toxicology, Faculty of Pharmacy, University of Veterinary and Pharmaceutical Sciences, Palackeho 1/3, 61242 Brno, Czech Republic. tereza.kauerova@gmail.com.
authors.forename: Tereza
authors.initials: T
authors.lastname: Kauerova
authors.affiliation: Department of Environmental Ecology, Faculty of Natural Sciences, Comenius University, Mlynska dolina Ch-2, 84215 Bratislava, Slovakia. matus.pesko@gmail.com.
authors.forename: Matus
authors.initials: M
authors.lastname: Pesko
authors.affiliation: Department of Chemical Drugs, Faculty of Pharmacy, University of Veterinary and Pharmaceutical Sciences, Palackeho 1/3, 61242 Brno, Czech Republic. jurd@email.cz.
authors.forename: Jiri
authors.initials: J
authors.lastname: Kos
authors.affiliation: Global Change Research Centre AS CR, Belidla 986/4a, 60300 Brno, Czech Republic. oravec.m@czechglobe.cz.
authors.forename: Michal
authors.initials: M
authors.lastname: Oravec
authors.affiliation: Department of Human Pharmacology and Toxicology, Faculty of Pharmacy, University of Veterinary and Pharmaceutical Sciences, Palackeho 1/3, 61242 Brno, Czech Republic. kollarp@vfu.cz.
authors.forename: Peter
authors.initials: P
authors.lastname: Kollar
authors.affiliation: Department of Biological Sciences, Cork Institute of Technology, Bishopstown, Cork, Ireland. aidan.coffey@cit.ie.
authors.forename: Aidan
authors.initials: A
authors.lastname: Coffey
authors.affiliation: Department of Biological Sciences, Cork Institute of Technology, Bishopstown, Cork, Ireland. jim.omahony@cit.ie.
authors.forename: Jim
authors.initials: J
authors.lastname: O'Mahony
authors.affiliation: Department of Infectious Diseases and Microbiology, Faculty of Veterinary Medicine, University of Veterinary and Pharmaceutical Sciences, Palackeho 1/3, 61242 Brno, Czech Republic. cizeka@vfu.cz.
authors.forename: Alois
authors.initials: A
authors.lastname: Cizek
authors.affiliation: Institute of Chemistry, Faculty of Natural Sciences, Comenius University, Mlynska dolina Ch-2, 84215 Bratislava, Slovakia. kata.kralova@gmail.com.
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, 61242 Brno, Czech Republic. josef.jampilek@gmail.com.
authors.forename: Josef
authors.initials: J
authors.lastname: Jampilek
mesh_terms: D000667:Ampicillin / Q000494:pharmacology; D000813:Anilides / Q000138:chemical synthesis / Q000494:pharmacology*; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000494:pharmacology*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D002736:Chloroplasts / Q000187:drug effects / Q000502:physiology; D004579:Electron Transport / Q000187:drug effects / Q000502:physiology; D006801:Humans; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects / Q000254:growth & development; D008826:Microbial Sensitivity Tests; D050296:Microbial Viability / Q000187:drug effects; D009000:Monocytes / Q000166:cytology / Q000187:drug effects; D016927:Mycobacterium avium subsp. paratuberculosis / Q000187:drug effects / Q000254:growth & development; D009169:Mycobacterium tuberculosis / Q000187:drug effects / Q000254:growth & development; D009281:Naphthalenes / Q000138:chemical synthesis / Q000494:pharmacology*; D010788:Photosynthesis / Q000187:drug effects / Q000502:physiology; D012293:Rifampin / Q000494:pharmacology; D018724:Spinacia oleracea / Q000187:drug effects / Q000502:physiology; D013329:Structure-Activity Relationship
chemical_list: D000813:Anilides; D000900:Anti-Bacterial Agents; D009281:Naphthalenes; D000667:Ampicillin; D012293:Rifampin
keywords: hydroxynaphthalene-2-carboxanilides; in vitro antibacterial activity; in vitro antimycobacterial activity; in vitro cytotoxicity; photosynthetic electron transport inhibition; structure-activity relationships