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In vitro and in vivo anti-inflammatory active copper(II)-lawsone complexes
We report in vitro and in vivo anti-inflammatory activities of a series of copper(II)-lawsone complexes of the general composition [Cu(Law)(2)(L(N))(x)(H(2)O)((2-x))]·yH(2)O; where HLaw = 2-hydroxy-1,4-naphthoquinone, x = 1 when L(N) = pyridine (1) and 2-aminopyridine (3) and x = 2 when L(N) = imida...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5526570/ https://www.ncbi.nlm.nih.gov/pubmed/28742852 http://dx.doi.org/10.1371/journal.pone.0181822 |
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author | Vančo, Ján Trávníček, Zdeněk Hošek, Jan Suchý, Pavel |
author_facet | Vančo, Ján Trávníček, Zdeněk Hošek, Jan Suchý, Pavel |
author_sort | Vančo, Ján |
collection | PubMed |
description | We report in vitro and in vivo anti-inflammatory activities of a series of copper(II)-lawsone complexes of the general composition [Cu(Law)(2)(L(N))(x)(H(2)O)((2-x))]·yH(2)O; where HLaw = 2-hydroxy-1,4-naphthoquinone, x = 1 when L(N) = pyridine (1) and 2-aminopyridine (3) and x = 2 when L(N) = imidazole (2), 3-aminopyridine (4), 4-aminopyridine (5), 3-hydroxypyridine (6), and 3,5-dimethylpyrazole (7). The compounds were thoroughly characterized by physical techniques, including single crystal X-ray analysis of complex 2. Some of the complexes showed the ability to suppress significantly the activation of nuclear factor κB (NF-κB) both by lipopolysaccharide (LPS) and TNF-alpha (complexes 3–7 at 100 nM level) in the similar manner as the reference drug prednisone (at 1 μM level). On the other hand, all the complexes 1–7 decreased significantly the levels of the secreted TNF-alpha after the LPS activation of THP-1 cells, thus showing the anti-inflammatory potential via both NF-κB moderation and by other mechanisms, such as influence on TNF-alpha transcription and/or translation and/or secretion. In addition, a strong intracellular pro-oxidative effect of all the complexes has been found at 100 nM dose in vitro. The ability to suppress the inflammatory response, caused by the subcutaneous application of λ-carrageenan, has been determined by in vivo testing in hind-paw edema model on rats. The most active complexes 1–3 (applied in a dose corresponding to 40 μmol Cu/kg), diminished the formation of edema simalarly as the reference drug indomethacine (applied in 10 mg/kg dose). The overall effect of the complexes, dominantly 1–3, shows similarity to anti-inflammatory drug benoxaprofen, known to induce intracellular pro-oxidative effects. |
format | Online Article Text |
id | pubmed-5526570 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-55265702017-08-07 In vitro and in vivo anti-inflammatory active copper(II)-lawsone complexes Vančo, Ján Trávníček, Zdeněk Hošek, Jan Suchý, Pavel PLoS One Research Article We report in vitro and in vivo anti-inflammatory activities of a series of copper(II)-lawsone complexes of the general composition [Cu(Law)(2)(L(N))(x)(H(2)O)((2-x))]·yH(2)O; where HLaw = 2-hydroxy-1,4-naphthoquinone, x = 1 when L(N) = pyridine (1) and 2-aminopyridine (3) and x = 2 when L(N) = imidazole (2), 3-aminopyridine (4), 4-aminopyridine (5), 3-hydroxypyridine (6), and 3,5-dimethylpyrazole (7). The compounds were thoroughly characterized by physical techniques, including single crystal X-ray analysis of complex 2. Some of the complexes showed the ability to suppress significantly the activation of nuclear factor κB (NF-κB) both by lipopolysaccharide (LPS) and TNF-alpha (complexes 3–7 at 100 nM level) in the similar manner as the reference drug prednisone (at 1 μM level). On the other hand, all the complexes 1–7 decreased significantly the levels of the secreted TNF-alpha after the LPS activation of THP-1 cells, thus showing the anti-inflammatory potential via both NF-κB moderation and by other mechanisms, such as influence on TNF-alpha transcription and/or translation and/or secretion. In addition, a strong intracellular pro-oxidative effect of all the complexes has been found at 100 nM dose in vitro. The ability to suppress the inflammatory response, caused by the subcutaneous application of λ-carrageenan, has been determined by in vivo testing in hind-paw edema model on rats. The most active complexes 1–3 (applied in a dose corresponding to 40 μmol Cu/kg), diminished the formation of edema simalarly as the reference drug indomethacine (applied in 10 mg/kg dose). The overall effect of the complexes, dominantly 1–3, shows similarity to anti-inflammatory drug benoxaprofen, known to induce intracellular pro-oxidative effects. Public Library of Science 2017-07-25 /pmc/articles/PMC5526570/ /pubmed/28742852 http://dx.doi.org/10.1371/journal.pone.0181822 Text en © 2017 Vančo et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Article Vančo, Ján Trávníček, Zdeněk Hošek, Jan Suchý, Pavel In vitro and in vivo anti-inflammatory active copper(II)-lawsone complexes |
title | In vitro and in vivo anti-inflammatory active copper(II)-lawsone complexes |
title_full | In vitro and in vivo anti-inflammatory active copper(II)-lawsone complexes |
title_fullStr | In vitro and in vivo anti-inflammatory active copper(II)-lawsone complexes |
title_full_unstemmed | In vitro and in vivo anti-inflammatory active copper(II)-lawsone complexes |
title_short | In vitro and in vivo anti-inflammatory active copper(II)-lawsone complexes |
title_sort | in vitro and in vivo anti-inflammatory active copper(ii)-lawsone complexes |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5526570/ https://www.ncbi.nlm.nih.gov/pubmed/28742852 http://dx.doi.org/10.1371/journal.pone.0181822 |
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