Antimycobacterial and herbicidal activity of ring-substituted 1-hydroxynaphthalene-2-carboxanilides.
In this study, a series of 22 ring-substituted 1-hydroxynaphthalene-2-carboxanilides were prepared and characterized. Primary in vitro screening of the synthesized compounds was performed against Mycobacterium marinum, Mycobacterium kansasii and Mycobacterium smegmatis. The compounds were also tested for their activity related to inhibition of photosynthetic electron transport (PET) in spinach (Spinacia oleracea L.) chloroplasts. Most of tested compounds showed the antimycobacterial activity against the three strains comparable or higher than the standard isoniazid. N-(3-Fluorophenyl)-1-hydroxynaphthalene-2-carboxamide showed the highest biological activity (MIC=28.4μmol/L) against M. marinum, N-(4-fluorophenyl)-1-hydroxynaphthalene-2-carboxamide showed the highest biological activity (MIC=14.2μmol/L) against M. kansasii, and N-(4-bromophenyl)-1-hydroxynaphthalene-2-carboxamide expressed the highest biological activity (MIC=46.7μmol/L) against M. smegmatis. This compound and 1-hydroxy-N-(3-methylphenyl)naphthalene-2-carboxamide were the most active compounds against all three tested strains. The PET inhibition expressed by IC50 value of the most active compound 1-hydroxy-N-(3-trifluoromethylphenyl)naphthalene-2-carboxamide was 5.3μmol/L. The most effective compounds demonstrated insignificant toxicity against the human monocytic leukemia THP-1 cell line. For all compounds, structure-activity relationships are discussed.
Department of Chemical Drugs, Faculty of Pharmacy, University of Veterinary and Pharmaceutical Sciences, Palackeho 1/3, 612 42 Brno, Czech Republic.
Tomas
T
Gonec
Jiri
J
Kos
Iveta
I
Zadrazilova
Matus
M
Pesko
Stanislava
S
Keltosova
Jan
J
Tengler
Pavel
P
Bobal
Peter
P
Kollar
Alois
A
Cizek
Katarina
K
Kralova
Josef
J
Jampilek
D000813:Anilides / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002736:Chloroplasts / Q000187:drug effects / Q000378:metabolism; D004579:Electron Transport / Q000187:drug effects; D006540:Herbicides / Q000138:chemical synthesis / Q000737:chemistry* / Q000633:toxicity; D006801:Humans; D008826:Microbial Sensitivity Tests; D009161:Mycobacterium / Q000187:drug effects; D009281:Naphthalenes / Q000737:chemistry*; D010788:Photosynthesis / Q000187:drug effects; D018724:Spinacia oleracea / Q000378:metabolism; D013329:Structure-Activity Relationship
D000813:Anilides; D000900:Anti-Bacterial Agents; D006540:Herbicides; D009281:Naphthalenes; C031721:naphthalene
Hydroxynaphthalene-2-carboxanilides; In vitro antimycobacterial activity; In vitro cytotoxicity; Lipophilicity; Photosynthetic electron transport inhibition; Spinach chloroplasts; Structure–activity relationships