PUBLICATION
A Gold(I) Phosphine Complex Containing Naphthalimide Ligand Functions as a TrxR Inhibiting Antiproliferative Agent and Angiogenesis Inhibitor
- Authors
- Ott, I., Qian, X., Xu, Y., Vlecken, D.H., Marques, I.J., Kubutat, D., Will, J., Sheldrick, W.S., Jesse, P., Prokop, A., and Bagowski, C.P.
- ID
- ZDB-PUB-090112-2
- Date
- 2009
- Source
- Journal of medicinal chemistry 52(3): 763-770 (Journal)
- Registered Authors
- Bagowski, Christoph P.
- Keywords
- none
- MeSH Terms
-
- Angiogenesis Inhibitors/chemical synthesis*
- Angiogenesis Inhibitors/pharmacology*
- Animals
- Antineoplastic Agents/chemical synthesis*
- Antineoplastic Agents/pharmacology*
- Apoptosis/drug effects
- Embryo, Nonmammalian/drug effects
- HT29 Cells
- Humans
- Maximum Tolerated Dose
- Microscopy, Confocal
- Organogold Compounds/chemical synthesis*
- Organogold Compounds/pharmacology*
- Tandem Mass Spectrometry
- Thioredoxin-Disulfide Reductase/antagonists & inhibitors*
- Zebrafish
- PubMed
- 19123857 Full text @ J. Med. Chem.
Citation
Ott, I., Qian, X., Xu, Y., Vlecken, D.H., Marques, I.J., Kubutat, D., Will, J., Sheldrick, W.S., Jesse, P., Prokop, A., and Bagowski, C.P. (2009) A Gold(I) Phosphine Complex Containing Naphthalimide Ligand Functions as a TrxR Inhibiting Antiproliferative Agent and Angiogenesis Inhibitor. Journal of medicinal chemistry. 52(3):763-770.
Abstract
The novel luminescent gold(I) complex [N-(N',N'-dimethylaminoethyl)-1,8-naphthalimide-4-sulfide](triethylphosphine)gold(I) was prepared and investigated for its primary biological properties. Cell culture experiments revealed strong antiproliferative effects and induction of apoptosis via mitochondrial pathways. Biodistribution studies by fluorescence microscopy and atomic absorption spectroscopy showed the uptake into cell organelles, an accumulation in the nuclei of tumor cells, and a homogeneous distribution in zebrafish embryos. In vivo monitoring of vascularisation in developing zebrafish embryos revealed a significant anti-angiogenic potency of the complex. Mechanistic experiments indicated that the inhibition of thioredoxin reductase (based on the covalent binding of a gold triethylphosphine fragment) might be involved in the pharmacodynamic behavior of this novel gold species.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping