title: N-Alkoxyphenylhydroxynaphthalenecarboxamides and Their Antimycobacterial Activity.
abstract: A series of nineteen N-(alkoxyphenyl)-2-hydroxynaphthalene-1-carboxamides and a series of their nineteen positional isomers N-(alkoxyphenyl)-1-hydroxynaphthalene-2-carboxamides were prepared and characterized. Primary in vitro screening of all the synthesized compounds was performed against Mycobacterium tuberculosis H37Ra, M. kansasii and M. smegmatis. Screening of the cytotoxicity of the compounds was performed using human monocytic leukemia THP-1 cells. Some of the tested compounds showed antimycobacterial activity comparable with or higher than that of rifampicin. For example, 2-hydroxy-N-(4-propoxyphenyl)-naphthalene-1-carboxamide showed the highest activity (MIC = 12 µM) against M. tuberculosis with insignificant cytotoxicity. N-[3-(But-2-yloxy)phenyl]- and N-[4-(but-2-yloxy)phenyl]-2-hydroxy-naphthalene-1-carboxamide demonstrated high activity against all tested mycobacterial strains and insignificant cytotoxicity. N-(Alkoxyphenyl)-1-hydroxynaphthalene-2-carboxamides demonstrated rather high effect against M. smegmatis and M. kansasii and strong antiproliferative effect against the human THP-1 cell line. Lipophilicity was found as the main physicochemical parameter influencing the activity. A significant decrease of mycobacterial cell metabolism (viability of M. tuberculosis H37Ra) was observed using MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide) assay. Structure-activity relationships are discussed.
authors.affiliation: Department of Chemical Drugs, Faculty of Pharmacy, University of Veterinary and Pharmaceutical Sciences, Palackeho 1, Brno 61242, Czech Republic. t.gonec@seznam.cz.
authors.forename: Tomas
authors.initials: T
authors.lastname: Gonec
authors.affiliation: Department of Infectious Diseases and Microbiology, Faculty of Veterinary Medicine, University of Veterinary and Pharmaceutical Sciences, Palackeho 1, Brno 61242, Czech Republic. sharka.pospisilova@gmail.com.
authors.forename: Sarka
authors.initials: S
authors.lastname: Pospisilova
authors.affiliation: Department of Human Pharmacology and Toxicology, Faculty of Pharmacy, University of Veterinary and Pharmaceutical Sciences, Palackeho 1, Brno 61242, Czech Republic. tereza.kauerova@gmail.com.
authors.forename: Tereza
authors.initials: T
authors.lastname: Kauerova
authors.affiliation: Department of Chemical Drugs, Faculty of Pharmacy, University of Veterinary and Pharmaceutical Sciences, Palackeho 1, Brno 61242, Czech Republic. jurd@email.cz.
authors.forename: Jiri
authors.initials: J
authors.lastname: Kos
authors.affiliation: Central Laboratories, Faculty of Chemical and Food Technology, Slovak University of Technology in Bratislava, Radlinskeho 9, Bratislava 81237, Slovakia. jana.dohanosova@stuba.sk.
authors.forename: Jana
authors.initials: J
authors.lastname: Dohanosova
authors.affiliation: Global Change Research Institute CAS, Belidla 986/4a, Brno 60300, 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, Brno 61242, 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: Central Laboratories, Faculty of Chemical and Food Technology, Slovak University of Technology in Bratislava, Radlinskeho 9, Bratislava 81237, Slovakia. tibor.liptaj@stuba.sk.
authors.forename: Tibor
authors.initials: T
authors.lastname: Liptaj
authors.affiliation: Department of Infectious Diseases and Microbiology, Faculty of Veterinary Medicine, University of Veterinary and Pharmaceutical Sciences, Palackeho 1, Brno 61242, Czech Republic. cizeka@vfu.cz.
authors.forename: Alois
authors.initials: A
authors.lastname: Cizek
authors.affiliation: Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Comenius University, Odbojarov 10, Bratislava 83232, Slovakia. josef.jampilek@gmail.com.
authors.forename: Josef
authors.initials: J
authors.lastname: Jampilek
mesh_terms: D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D006801:Humans; D008826:Microbial Sensitivity Tests; D050296:Microbial Viability / Q000187:drug effects*; D015394:Molecular Structure; D019909:Mycobacterium kansasii / Q000187:drug effects; D020102:Mycobacterium smegmatis / Q000187:drug effects; D009169:Mycobacterium tuberculosis / Q000187:drug effects; D009284:Naphthols / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D000900:Anti-Bacterial Agents; D009284:Naphthols
keywords: MTT assay; hydroxynaphthalenecarboxamides; in vitro antimycobacterial activity; lipophilicity; structure-activity relationships