New Gold(I) Organometallic Compounds with Biological Activity in Cancer Cells
New Gold(I) Organometallic Compounds with Biological Activity in Cancer Cells
复制标题
DOI：
10.1002/ejic.201402248
复制
发表时间：
2014-09-01
影响因子：
2.3
通讯作者：
Casini, Angela
中科院分区：
文献类型：
--
作者：
Bertrand, Benoit;de Almeida, Andreia;Casini, Angela
合成了含荧光配体香豆素的N-杂环卡宾金（I）配合物，并通过各种技术进行了表征。这些化合物在体外正常细胞和肿瘤细胞中的抗增殖作用进行了检查，它们表现出中等活性和一定程度的选择性。这些化合物还显示出有效抑制硒酶硫氧还蛋白还原酶（TrxR），而它们对谷胱甘肽还原酶（GR）和谷胱甘肽过氧化物酶的有效性较差。值得注意的是，{3-[（7-甲氧基-2-氧代-2H-色烯-4-基）甲基]-1-甲基咪唑-2-亚基}（四-O-乙酰基-1-硫代-β-D-吡喃葡萄糖苷）金（I）（3）在细胞提取物中也显示出对TrxR的显著抑制，并且似乎激活GR。来自生物素偶联碘乙酰胺测定的系统的机制信息显示出与硒代半胱氨酸残基的选择性金属结合。初步的共聚焦荧光显微镜实验证明，3进入肿瘤细胞，在那里它到达核区室。
N-Heterocyclic carbene gold(I) complexes bearing a fluorescent coumarin ligand were synthesized and characterized by various techniques. The compounds were examined for their antiproliferative effects in normal and tumor cells in vitro; they demonstrated moderate activity and a certain degree of selectivity. The compounds were also shown to efficiently inhibit the selenoenzyme thioredoxin reductase (TrxR), whereas they were poorly effective towards the glutathione reductase (GR) and glutathione peroxidase enzymes. Notably, {3-[(7-methoxy-2-oxo-2H-chromen-4-yl) methyl]-1-methylimidazol-2-ylidene}(tetra-O-acetyl-1-thio-beta-D-glucopyranosido) gold(I) (3) showed a pronounced inhibition of TrxR also in cell extracts, and it appeared to activate GR. Mechanistic information on the system derived from biotinconjugated iodoacetamide assays showed selective metal binding to selenocysteine residues. Preliminary confocal fluorescence microscopy experiments proved that 3 enters tumor cells, where it reaches the nuclear compartment.