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Effect of 2-Chloro-Substitution of Adenine Moiety in Mixed-Ligand Gold(I) Triphenylphosphine Complexes on Anti-Inflammatory Activity: The Discrepancy between the In Vivo and In Vitro Models

A series of gold(I) triphenylphosphine (PPh(3)) complexes (1–9) involving 2-chloro-N6-(substituted-benzyl)adenine derivatives as N-donor ligands was synthesized and thoroughly characterized by relevant methods, including electrospray-ionization (ESI) mass spectrometry and multinuclear NMR spectrosco...

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Autores principales: Hošek, Jan, Vančo, Ján, Štarha, Pavel, Paráková, Lenka, Trávníček, Zdeněk
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3842384/
https://www.ncbi.nlm.nih.gov/pubmed/24312423
http://dx.doi.org/10.1371/journal.pone.0082441
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author Hošek, Jan
Vančo, Ján
Štarha, Pavel
Paráková, Lenka
Trávníček, Zdeněk
author_facet Hošek, Jan
Vančo, Ján
Štarha, Pavel
Paráková, Lenka
Trávníček, Zdeněk
author_sort Hošek, Jan
collection PubMed
description A series of gold(I) triphenylphosphine (PPh(3)) complexes (1–9) involving 2-chloro-N6-(substituted-benzyl)adenine derivatives as N-donor ligands was synthesized and thoroughly characterized by relevant methods, including electrospray-ionization (ESI) mass spectrometry and multinuclear NMR spectroscopy. The anti-inflammatory and antiedematous effects of three representatives 1, 5 and 9 were evaluated by means of in vitro model based on the expression of pro- and anti-inflammatory cytokines and influence of the complexes on selected forms of matrix metalloproteinases secreted by LPS-activated THP-1 monocytes and in vivo model evaluating the antiedematous effect of the complexes in the carrageenan-induced rat hind-paw edema model. In addition to the pharmacological observations, the affected hind paws were post mortem subjected to histological and immunohistochemical evaluations. The results of both in vivo and ex vivo methods revealed low antiedematous and anti-inflammatory effects of the complexes, even though the in vitro model identified them as promising anti-inflammatory acting compounds. The reason for this discrepancy lies probably in low stability of the studied complexes in biological environment, as demonstrated by the solution interaction studies with sulfur-containing biomolecules (cysteine and reduced glutathione) using the ESI mass spectrometry.
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spelling pubmed-38423842013-12-05 Effect of 2-Chloro-Substitution of Adenine Moiety in Mixed-Ligand Gold(I) Triphenylphosphine Complexes on Anti-Inflammatory Activity: The Discrepancy between the In Vivo and In Vitro Models Hošek, Jan Vančo, Ján Štarha, Pavel Paráková, Lenka Trávníček, Zdeněk PLoS One Research Article A series of gold(I) triphenylphosphine (PPh(3)) complexes (1–9) involving 2-chloro-N6-(substituted-benzyl)adenine derivatives as N-donor ligands was synthesized and thoroughly characterized by relevant methods, including electrospray-ionization (ESI) mass spectrometry and multinuclear NMR spectroscopy. The anti-inflammatory and antiedematous effects of three representatives 1, 5 and 9 were evaluated by means of in vitro model based on the expression of pro- and anti-inflammatory cytokines and influence of the complexes on selected forms of matrix metalloproteinases secreted by LPS-activated THP-1 monocytes and in vivo model evaluating the antiedematous effect of the complexes in the carrageenan-induced rat hind-paw edema model. In addition to the pharmacological observations, the affected hind paws were post mortem subjected to histological and immunohistochemical evaluations. The results of both in vivo and ex vivo methods revealed low antiedematous and anti-inflammatory effects of the complexes, even though the in vitro model identified them as promising anti-inflammatory acting compounds. The reason for this discrepancy lies probably in low stability of the studied complexes in biological environment, as demonstrated by the solution interaction studies with sulfur-containing biomolecules (cysteine and reduced glutathione) using the ESI mass spectrometry. Public Library of Science 2013-11-27 /pmc/articles/PMC3842384/ /pubmed/24312423 http://dx.doi.org/10.1371/journal.pone.0082441 Text en © 2013 Hosek 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, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Hošek, Jan
Vančo, Ján
Štarha, Pavel
Paráková, Lenka
Trávníček, Zdeněk
Effect of 2-Chloro-Substitution of Adenine Moiety in Mixed-Ligand Gold(I) Triphenylphosphine Complexes on Anti-Inflammatory Activity: The Discrepancy between the In Vivo and In Vitro Models
title Effect of 2-Chloro-Substitution of Adenine Moiety in Mixed-Ligand Gold(I) Triphenylphosphine Complexes on Anti-Inflammatory Activity: The Discrepancy between the In Vivo and In Vitro Models
title_full Effect of 2-Chloro-Substitution of Adenine Moiety in Mixed-Ligand Gold(I) Triphenylphosphine Complexes on Anti-Inflammatory Activity: The Discrepancy between the In Vivo and In Vitro Models
title_fullStr Effect of 2-Chloro-Substitution of Adenine Moiety in Mixed-Ligand Gold(I) Triphenylphosphine Complexes on Anti-Inflammatory Activity: The Discrepancy between the In Vivo and In Vitro Models
title_full_unstemmed Effect of 2-Chloro-Substitution of Adenine Moiety in Mixed-Ligand Gold(I) Triphenylphosphine Complexes on Anti-Inflammatory Activity: The Discrepancy between the In Vivo and In Vitro Models
title_short Effect of 2-Chloro-Substitution of Adenine Moiety in Mixed-Ligand Gold(I) Triphenylphosphine Complexes on Anti-Inflammatory Activity: The Discrepancy between the In Vivo and In Vitro Models
title_sort effect of 2-chloro-substitution of adenine moiety in mixed-ligand gold(i) triphenylphosphine complexes on anti-inflammatory activity: the discrepancy between the in vivo and in vitro models
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3842384/
https://www.ncbi.nlm.nih.gov/pubmed/24312423
http://dx.doi.org/10.1371/journal.pone.0082441
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