TY - JOUR
T1 - A gold(I) phosphine complex containing a naphthalimide ligand functions as a TrxR inhibiting antiproliferative agent and angiogenesis inhibitor
AU - Ott, Ingo
AU - Qian, Xuhong
AU - Xu, Yufang
AU - Vlecken, Danielle H.W.
AU - Marques, Ines J.
AU - Kubutat, Dominic
AU - Will, Joanna
AU - Sheldrick, William S.
AU - Jesse, Patrick
AU - Prokop, Aram
AU - Bagowski, Christoph P.
PY - 2009/2/12
Y1 - 2009/2/12
N2 - The novel luminescent gold(I) complex [N-(N'N'-dimethylaminoethyl)-1,8- naphthalimide-4-sulflde](trieth- ylphosphine)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.
AB - The novel luminescent gold(I) complex [N-(N'N'-dimethylaminoethyl)-1,8- naphthalimide-4-sulflde](trieth- ylphosphine)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.
UR - https://www.scopus.com/pages/publications/61449155600
U2 - 10.1021/jm8012135
DO - 10.1021/jm8012135
M3 - 文章
C2 - 19123857
AN - SCOPUS:61449155600
SN - 0022-2623
VL - 52
SP - 763
EP - 770
JO - Journal of Medicinal Chemistry
JF - Journal of Medicinal Chemistry
IS - 3
ER -