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Gold(I)-Triphenylphosphine Complexes with Hypoxanthine-Derived Ligands: In Vitro Evaluations of Anticancer and Anti-Inflammatory Activities
A series of gold(I) complexes involving triphenylphosphine (PPh(3)) and one N-donor ligand derived from deprotonated mono- or disubstituted hypoxanthine (HL(n)) of the general composition [Au(L(n))(PPh(3))] (1–9) is reported. The complexes were thoroughly characterized, including multinuclear high r...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4167326/ https://www.ncbi.nlm.nih.gov/pubmed/25226034 http://dx.doi.org/10.1371/journal.pone.0107373 |
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author | Křikavová, Radka Hošek, Jan Vančo, Ján Hutyra, Jakub Dvořák, Zdeněk Trávníček, Zdeněk |
author_facet | Křikavová, Radka Hošek, Jan Vančo, Ján Hutyra, Jakub Dvořák, Zdeněk Trávníček, Zdeněk |
author_sort | Křikavová, Radka |
collection | PubMed |
description | A series of gold(I) complexes involving triphenylphosphine (PPh(3)) and one N-donor ligand derived from deprotonated mono- or disubstituted hypoxanthine (HL(n)) of the general composition [Au(L(n))(PPh(3))] (1–9) is reported. The complexes were thoroughly characterized, including multinuclear high resolution NMR spectroscopy as well as single crystal X-ray analysis (for complexes 1 and 3). The complexes were screened for their in vitro cytotoxicity against human cancer cell lines MCF7 (breast carcinoma), HOS (osteosarcoma) and THP-1 (monocytic leukaemia), which identified the complexes 4–6 as the most promising representatives, who antiproliferative activity was further tested against A549 (lung adenocarcinoma), G-361 (melanoma), HeLa (cervical cancer), A2780 (ovarian carcinoma), A2780R (ovarian carcinoma resistant to cisplatin), 22Rv1 (prostate cancer) cell lines. Complexes 4–6 showed a significantly higher in vitro anticancer effect against the employed cancer cells, except for G-361, as compared with the commercially used anticancer drug cisplatin, with IC(50) ≈ 1–30 µM. Anti-inflammatory activity was evaluated in vitro by the assessment of the ability of the complexes to modulate secretion of the pro-inflammatory cytokines, i.e. tumour necrosis factor-α (TNF-α) and interleukin-1β (IL-1β), in the lipopolysaccharide-activated macrophage-like THP-1 cell model. The results of this study identified the complexes as auspicious anti-inflammatory agents with similar or better activity as compared with the clinically applied gold-based antiarthritic drug Auranofin. In an effort to explore the possible mechanisms responsible for the biological effect, the products of interactions of selected complexes with sulfur-containing biomolecules (L-cysteine and reduced glutathione) were studied by means of the mass-spectrometry study. |
format | Online Article Text |
id | pubmed-4167326 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-41673262014-09-22 Gold(I)-Triphenylphosphine Complexes with Hypoxanthine-Derived Ligands: In Vitro Evaluations of Anticancer and Anti-Inflammatory Activities Křikavová, Radka Hošek, Jan Vančo, Ján Hutyra, Jakub Dvořák, Zdeněk Trávníček, Zdeněk PLoS One Research Article A series of gold(I) complexes involving triphenylphosphine (PPh(3)) and one N-donor ligand derived from deprotonated mono- or disubstituted hypoxanthine (HL(n)) of the general composition [Au(L(n))(PPh(3))] (1–9) is reported. The complexes were thoroughly characterized, including multinuclear high resolution NMR spectroscopy as well as single crystal X-ray analysis (for complexes 1 and 3). The complexes were screened for their in vitro cytotoxicity against human cancer cell lines MCF7 (breast carcinoma), HOS (osteosarcoma) and THP-1 (monocytic leukaemia), which identified the complexes 4–6 as the most promising representatives, who antiproliferative activity was further tested against A549 (lung adenocarcinoma), G-361 (melanoma), HeLa (cervical cancer), A2780 (ovarian carcinoma), A2780R (ovarian carcinoma resistant to cisplatin), 22Rv1 (prostate cancer) cell lines. Complexes 4–6 showed a significantly higher in vitro anticancer effect against the employed cancer cells, except for G-361, as compared with the commercially used anticancer drug cisplatin, with IC(50) ≈ 1–30 µM. Anti-inflammatory activity was evaluated in vitro by the assessment of the ability of the complexes to modulate secretion of the pro-inflammatory cytokines, i.e. tumour necrosis factor-α (TNF-α) and interleukin-1β (IL-1β), in the lipopolysaccharide-activated macrophage-like THP-1 cell model. The results of this study identified the complexes as auspicious anti-inflammatory agents with similar or better activity as compared with the clinically applied gold-based antiarthritic drug Auranofin. In an effort to explore the possible mechanisms responsible for the biological effect, the products of interactions of selected complexes with sulfur-containing biomolecules (L-cysteine and reduced glutathione) were studied by means of the mass-spectrometry study. Public Library of Science 2014-09-16 /pmc/articles/PMC4167326/ /pubmed/25226034 http://dx.doi.org/10.1371/journal.pone.0107373 Text en © 2014 Křikavová 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 Křikavová, Radka Hošek, Jan Vančo, Ján Hutyra, Jakub Dvořák, Zdeněk Trávníček, Zdeněk Gold(I)-Triphenylphosphine Complexes with Hypoxanthine-Derived Ligands: In Vitro Evaluations of Anticancer and Anti-Inflammatory Activities |
title | Gold(I)-Triphenylphosphine Complexes with Hypoxanthine-Derived Ligands: In Vitro Evaluations of Anticancer and Anti-Inflammatory Activities |
title_full | Gold(I)-Triphenylphosphine Complexes with Hypoxanthine-Derived Ligands: In Vitro Evaluations of Anticancer and Anti-Inflammatory Activities |
title_fullStr | Gold(I)-Triphenylphosphine Complexes with Hypoxanthine-Derived Ligands: In Vitro Evaluations of Anticancer and Anti-Inflammatory Activities |
title_full_unstemmed | Gold(I)-Triphenylphosphine Complexes with Hypoxanthine-Derived Ligands: In Vitro Evaluations of Anticancer and Anti-Inflammatory Activities |
title_short | Gold(I)-Triphenylphosphine Complexes with Hypoxanthine-Derived Ligands: In Vitro Evaluations of Anticancer and Anti-Inflammatory Activities |
title_sort | gold(i)-triphenylphosphine complexes with hypoxanthine-derived ligands: in vitro evaluations of anticancer and anti-inflammatory activities |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4167326/ https://www.ncbi.nlm.nih.gov/pubmed/25226034 http://dx.doi.org/10.1371/journal.pone.0107373 |
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