A Gold(III) Pincer Ligand Scaffold for the Synthesis of Binuclear and Bioconjugated Complexes: Synthesis and Anticancer Potential
A Gold(III) Pincer Ligand Scaffold for the Synthesis of Binuclear and Bioconjugated Complexes: Synthesis and Anticancer Potential
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DOI：
10.1002/chem.201705902
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发表时间：
2018-03-07
影响因子：
4.3
通讯作者：
Bochmann, Manfred
中科院分区：
文献类型：
--
作者：
Bertrand, Benoit;O'Connell, Maria A.;Bochmann, Manfred
含有功能化N-杂环卡宾(NHC)配体的环金属化金-III络合物为生物偶联和双核络合物提供了一条高产率的模块化路线。该方法已应用于生物素和17-乙炔基雌二醇载体生物共轭配合物的合成，以及双金属Au-III/Au-I配合物的合成。这些化合物对不同癌细胞株的体外抗增殖活性依赖于连接子的长度，其中较长的连接子最有效。雌二醇偶联物AUC(6)Estra对雌激素受体阳性(ER+)癌细胞的毒性大于对ER-癌细胞和非癌细胞的毒性。相对于健康细胞标准，双金属络合物AuC6Au对乳腺癌细胞的选择性比单金属络合物AuNHC更高。对表达或不表达生物素和雌激素受体的细胞的金属摄取研究表明，与非矢量化类似物AuNHC相比，生物结合络合物AUC(6)Biot和AUC(6)Estra的金的传递得到了改善和定向。利用FRET熔融技术研究生物偶联物和双金属络合物与人端粒G-四链DNA的相互作用，发现相对于非矢量化类似物AuNHC，稳定这种DNA结构的能力降低。
Cyclometalated (CNC)Au-III complexes bearing functionalized N-heterocyclic carbene (NHC) ligands provide a high-yielding, modular route to bioconjugated and binuclear complexes. This methodology has been applied to the synthesis of bioconjugated complexes presenting biotin and 17-ethynylestradiol vectors, as well as to the synthesis of bimetallic Au-III/Au-I complexes. The in vitro antiproliferative activities of these compounds against various cancer cells lines depend on the linker length, with the longer linker being the most potent. The estradiol conjugate AuC(6)Estra proved to be more toxic against the estrogen receptor positive (ER+) cancer cells than against the ER- cancer cells and non-cancer cells. The bimetallic complex AuC6Au was more selective for breast cancer cells with respect to a healthy cell standard than the monometallic complex AuNHC. The metal uptake study on cells expressing or not biotin and estrogen receptors revealed an improved and targeted delivery of gold for both the bioconjugated complexes AuC(6)Biot and AuC(6)Estra compared to the non-vectorised analogue AuNHC. The investigations of the interaction of the bioconjugates and bimetallic complexes with human telomeric G-quadruplex DNA using FRET-melting techniques revealed a reduced ability to stabilize this DNA structure with respect to the non-vectorised analogue AuNHC.