文献类型：期刊文献

英文题名：A Gold(I) Phosphine Complex Containing a Naphthalimide Ligand Functions as a TrxR Inhibiting Antiproliferative Agent and Angiogenesis Inhibitor

作者：Ott, Ingo[1,2];Qian, Xuhong[2];Xu, Yufang[2];Vlecken, Danielle H. W.[3];Marques, Ines J.[3];Kubutat, Dominic[4];Will, Joanna[4];Sheldrick, William S.[4];Jesse, Patrick[5];Prokop, Aram[5];Bagowski, Christoph P.[3]

机构：[1]Free Univ Berlin, Inst Pharm, D-14195 Berlin, Germany;[2]E China Univ Sci & Technol, Shanghai Key Lab Chem Biol, Shanghai 200237, Peoples R China;[3]Leiden Univ, Dept Integrat Zool, Inst Biol, Al Leiden, Netherlands;[4]Ruhr Univ Bochum, Lehrstuhl Analyt Chem, D-44780 Bochum, Germany;[5]Univ Med Ctr Charite Berlin, Dept Pediat Oncol Hematol, D-13353 Berlin, Germany

年份：2009

卷号：52

期号：3

起止页码：763

外文期刊名：JOURNAL OF MEDICINAL CHEMISTRY

收录：;WOS:【SCI-EXPANDED(收录号:WOS:000263142400019)】；

基金：Financial support by DFG-Deutsche Forschungsgemeinschaft (Project FOR-630), BMBF-Bundesministerium fur Bildung and Forschung (Project CHN 08/007), and the Portuguese Foundation for Science and Technology (Grant SFRH/BD/27262/2006) is gratefully acknowledged. We are also grateful for technical support by Heike Scheffler.

语种：英文

摘要：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.