Alkynyl gold(I) phosphane complexes: evaluation of structure-activity-relationships for the phosphane ligands, effects on key signaling proteins and preliminary in-vivo studies with a nanoformulated complex
| العنوان: | Alkynyl gold(I) phosphane complexes: evaluation of structure-activity-relationships for the phosphane ligands, effects on key signaling proteins and preliminary in-vivo studies with a nanoformulated complex |
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| المؤلفون: | Malte Kokoschka, Ingo Ott, Chi-Ming Che, Raymond Wai-Yin Sun, Heike Bunjes, Laura Rodríguez, Elisabet Aguiló, Katrin Göke, Stefan Wölfl, Vincent Andermark, Luciano Oehninger, Mohamed A. Abu el Maaty, Taotao Zou, Ching Tung Lum |
| المصدر: | Dipòsit Digital de la UB Universidad de Barcelona |
| بيانات النشر: | Springer Verlag, 2015. |
| سنة النشر: | 2015 |
| مصطلحات موضوعية: | Cell signaling, Lung Neoplasms, Thioredoxin-Disulfide Reductase, Stereochemistry, Cell Survival, Phosphines, Microarrays, Thioredoxin reductase, HSP27 Heat-Shock Proteins, Alkyne, Mice, Nude, Antineoplastic Agents, Or, Anisoles, 010402 general chemistry, Cell morphology, Ligands, 01 natural sciences, Biochemistry, Inorganic Chemistry, chemistry.chemical_compound, Mice, Structure-Activity Relationship, Coordination Complexes, Structure–activity relationship, Animals, Humans, Càncer, Heat-Shock Proteins, Cell Proliferation, Cancer, chemistry.chemical_classification, Mitogen-Activated Protein Kinase 1, Mice, Inbred BALB C, Mitogen-Activated Protein Kinase 3, 010405 organic chemistry, Chemistry, Ligand, Aryl, Protein microarrays, Cations, Monovalent, Xenograft Model Antitumor Assays, 0104 chemical sciences, Phosphorylation, Female, Gold, HT29 Cells, Organogold Compounds, Molecular Chaperones |
| الوصف: | Gold alkynyl complexes with phosphane ligands of the type (alkynyl)Au(I)(phosphane) represent a group of bioorganometallics, which has only recently been evaluated biologically in more detail. Structure-activity-relationship studies regarding the residues of the phosphane ligand (P(Ph)3, P(2-furyl)3, P(DAPTA)3, P(PTA)3, P(Et)3, P(Me)3) of complexes with an 4-ethynylanisole alkyne ligand revealed no strong differences concerning cytotoxicity. However, a relevant preference for the heteroatom free alkyl/aryl residues concerning inhibition of the target enzyme thioredoxin reductase was evident. Complex 1 with the triphenylphosphane ligand was selected for further studies, in which clear effects on cell morphology were monitored by time-lapse microscopy. Effects on cellular signaling were determined by ELISA microarrays and showed a significant induction of the phosphorylation of ERK1 (extracellular signal related kinase 1), ERK2 and HSP27 (heat shock protein 27) in HT-29 cells. Application of 1 in-vivo in a mouse xenograft model was found to be challenging due to the low solubility of the complex and required a formulation strategy based on a peanut oil nanoemulsion. |
| وصف الملف: | application/pdf |
| اللغة: | English |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::f6b0e0e51348481ddf02be39a500d40c http://hdl.handle.net/2445/152519 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....f6b0e0e51348481ddf02be39a500d40c |
| قاعدة البيانات: | OpenAIRE |
| الوصف غير متاح. |