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
Language English Country United States Media print-electronic
Document type Journal Article
PubMed
26850306
DOI
10.1016/j.jinorgbio.2015.12.020
PII: S0162-0134(15)30154-9
Knihovny.cz E-resources
- Keywords
- Alkyne, Cancer, Formulation, Gold, Microarray, Xenograft,
- MeSH
- Anisoles chemistry MeSH
- HT29 Cells MeSH
- Phosphines chemistry MeSH
- Cations, Monovalent MeSH
- Coordination Complexes chemical synthesis pharmacology MeSH
- Humans MeSH
- Ligands MeSH
- Mitogen-Activated Protein Kinase 1 genetics metabolism MeSH
- Mitogen-Activated Protein Kinase 3 genetics metabolism MeSH
- Molecular Chaperones MeSH
- Mice, Inbred BALB C MeSH
- Mice, Nude MeSH
- Mice MeSH
- Lung Neoplasms drug therapy pathology MeSH
- Organogold Compounds chemical synthesis pharmacology MeSH
- Cell Proliferation drug effects MeSH
- HSP27 Heat-Shock Proteins genetics metabolism MeSH
- Heat-Shock Proteins MeSH
- Antineoplastic Agents chemical synthesis pharmacology MeSH
- Thioredoxin-Disulfide Reductase antagonists & inhibitors genetics metabolism MeSH
- Cell Survival drug effects MeSH
- Structure-Activity Relationship MeSH
- Xenograft Model Antitumor Assays MeSH
- Gold chemistry MeSH
- Animals MeSH
- Check Tag
- Humans MeSH
- Mice MeSH
- Female MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Names of Substances
- Anisoles MeSH
- Phosphines MeSH
- HSPB1 protein, human MeSH Browser
- Cations, Monovalent MeSH
- Coordination Complexes MeSH
- Ligands MeSH
- MAPK1 protein, human MeSH Browser
- Mitogen-Activated Protein Kinase 1 MeSH
- Mitogen-Activated Protein Kinase 3 MeSH
- Molecular Chaperones MeSH
- Organogold Compounds MeSH
- phosphine MeSH Browser
- HSP27 Heat-Shock Proteins MeSH
- Heat-Shock Proteins MeSH
- Antineoplastic Agents MeSH
- Thioredoxin-Disulfide Reductase MeSH
- Gold MeSH
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.
References provided by Crossref.org
