Synthesis and Biological Evaluation of N-Alkoxyphenyl-3-hydroxynaphthalene-2-carboxanilides

0444472 - ÚVGZ 2016 RIV CH eng J - Journal Article
Goněc, T. - Zadražilová, I. - Nevin, E. - Kauerová, T. - Pesko, M. - Oravec, Michal - Kollár, P. - Coffey, A. - Mahony, J. O. - Čížek, A. - Králová, K. - Jampílek, J.
Synthesis and Biological Evaluation of N-Alkoxyphenyl-3-hydroxynaphthalene-2-carboxanilides.
Molecules. Roč. 20, č. 6 (2015), s. 9767-9787. E-ISSN 1420-3049
R&D Projects: GA MŠMT EE2.3.20.0246; GA MŠMT(CZ) LM2010007
Institutional support: RVO:67179843
Keywords : hydroxynaphthalene-2-carboxanilides * in vitro antibacterial activity * in vitro antimycobacterial activity * in vitro cytotoxicity * photosynthetic electron transport inhibition * structure-activity relationships
Subject RIV: EH - Ecology, Behaviour
Impact factor: 2.465, year: 2015

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.
Permanent Link: http://hdl.handle.net/11104/0247022