PUBLICATION
Mononuclear gold(III) complexes with phenanthroline ligands as efficient inhibitors of angiogenesis: A comparative study with auranofin and sunitinib
- Authors
- Pavic, A., Glišić, B.Đ., Vojnovic, S., Warżajtis, B., Savić, N.D., Antić, M., Radenković, S., Janjić, G.V., Nikodinovic-Runic, J., Rychlewska, U., Djuran, M.I.
- ID
- ZDB-PUB-170705-1
- Date
- 2017
- Source
- Journal of inorganic biochemistry 174: 156-168 (Journal)
- Registered Authors
- Keywords
- Angiogenesis, Cytotoxicity, Embryotoxicity, Gold(III) complexes, Phenanthroline
- MeSH Terms
-
- A549 Cells
- Angiogenesis Inhibitors/chemistry*
- Animals
- Auranofin/chemistry*
- HeLa Cells
- Humans
- Indoles/chemistry*
- Matrix Metalloproteinase 2/chemistry*
- Matrix Metalloproteinase 9/chemistry*
- Molecular Docking Simulation*
- Phenanthrolines/chemistry*
- Pyrroles/chemistry*
- Thioredoxin Reductase 1/chemistry*
- Vascular Endothelial Growth Factor Receptor-2/chemistry*
- Zebrafish
- PubMed
- 28675847 Full text @ J. Inorg. Biochem.
Citation
Pavic, A., Glišić, B.Đ., Vojnovic, S., Warżajtis, B., Savić, N.D., Antić, M., Radenković, S., Janjić, G.V., Nikodinovic-Runic, J., Rychlewska, U., Djuran, M.I. (2017) Mononuclear gold(III) complexes with phenanthroline ligands as efficient inhibitors of angiogenesis: A comparative study with auranofin and sunitinib. Journal of inorganic biochemistry. 174:156-168.
Abstract
Gold(III) complexes with 1,7- and 4,7-phenanthroline ligands, [AuCl3(1,7-phen-κN7)] (1) and [AuCl3(4,7-phen-κN4)] (2) were synthesized and structurally characterized by spectroscopic (NMR, IR and UV-vis) and single-crystal X-ray diffraction techniques. In these complexes, 1,7- and 4,7-phenanthrolines are monodentatedly coordinated to the Au(III) ion through the N7 and N4 nitrogen atoms, respectively. In comparison to the clinically relevant anti-angiogenic compounds auranofin and sunitinib, gold(III)-phenanthroline complexes showed from 1.5- to 20-fold higher anti-angiogenic potential, and 13- and 118-fold lower toxicity. Among the tested compounds, complex 1 was the most potent and may be an excellent anti-angiogenic drug candidate, since it showed strong anti-angiogenic activity in zebrafish embryos achieving IC50 value (concentration resulting in an anti-angiogenic phenotype at 50% of embryos) of 2.89μM, while had low toxicity with LC50 value (the concentration inducing the lethal effect of 50% embryos) of 128μM. Molecular docking study revealed that both complexes and ligands could suppress angiogenesis targeting the multiple major regulators of angiogenesis, such as the vascular endothelial growth factor receptor (VEGFR-2), the matrix metalloproteases (MMP-2 and MMP-9), and thioredoxin reductase (TrxR1), where the complexes showed higher binding affinity in comparison to ligands, and particularly to auranofin, but comparable to sunitinib, an anti-angiogenic drug of clinical relevance.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping