A Gold(I) Phosphine Complex Containing a Naphthalimide Ligand Functions as a TrxR Inhibiting Antiproliferative Agent and Angiogenesis Inhibitor
A Gold(I) Phosphine Complex Containing a Naphthalimide Ligand Functions as a TrxR Inhibiting Antiproliferative Agent and Angiogenesis Inhibitor
复制标题
含有萘酰亚胺配体的金 (I) 膦络合物可作为 TrxR 抑制性抗增殖剂和血管生成抑制剂
DOI：
10.1021/jm8012135
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发表时间：
2009-02-12
影响因子：
7.3
通讯作者：
Bagowski, Christoph P.
中科院分区：
文献类型：
--
作者：
Ott, Ingo;Qian, Xuhong;Bagowski, Christoph P.
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, all 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.
