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.
Disciplines
Biology
DOI
10.3390/molecules20069767
Full Publication Date
May 2015
Publisher
MDPI
Funder Name 1
Irish Department of Agrigulture, Fisheries and Food (FIRM)
Award Number 1
08RDCIT601 & 08RDCIT617
Resource Type
journal article
Access Rights
open access
License Condition
This work is licensed under a Creative Commons Attribution 4.0 International License.
Alternative Identifier
https://www.mdpi.com/1420-3049/20/6/9767/htm
Recommended Citation
Gonec, T. et al., 2015. Synthesis and Biological Evaluation of N-Alkoxyphenyl-3-hydroxynaphthalene-2-carboxanilides. Molecules, 20(6), pp.9767–9787. Available at: http://dx.doi.org/10.3390/molecules20069767.
Publication Details
Molecules
Copyright © 2015 Gonec, T. et al.
This study was supported by IGA VFU Brno 52/2014/FaF, 304/2015/FaF, 320/2015/FaF, 322/2015/FaF, 323/2015/FaF, by project APVV-0061-11, by the EfCOP-IPo project ENVIMET (CZ.1.07/2.3.00/20.0246) and by the Irish Department of Agriculture Fisheries and Food (FIRM): Refs 08RDCIT601 & 08RDCIT617. The system of high-performance liquid chromatography coupled to an LTQ Orbitrap XL high-resolution mass spectrometer forms a part of the National Infrastructure CzeCos/ICOS (LM2010007).