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Article

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Creative Commons Attribution 4.0 License
This work is licensed under a Creative Commons Attribution 4.0 License.

Disciplines

Biology

CIT Disciplines

1.6 BIOLOGICAL SCIENCES

Publication Details

Molecules

Copyright © 2016 Gonec, T. et al.

This study was supported by IGA VFU Brno 311/2016/FaF and 323/2015/FaF, the Slovak Grant Agency VEGA 1/0770/15, the Slovak Research and Development Agency (Grant No. APVV-0516-12) and by the Irish Department of Agriculture Fisheries and Food (FIRM): Refs 08RDCIT601 & 08RDCIT617. The HPLC/HRMS system forms a part of the National Infrastructure CzeCOS (LM2015061); Michal Oravec was supported by the National Sustainability Program (NPU I; Grant No. LO1415 POLYMAT).

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.

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