Cytotoxicity of cyclometalated platinum complexes based on tridentate NCN and CNN-coordinating ligands: remarkable coordination dependence.
Cytotoxicity of cyclometalated platinum complexes based on tridentate NCN and CNN-coordinating ligands: remarkable coordination dependence.
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DOI：
10.1016/j.jinorgbio.2014.01.021
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发表时间：
2014-05
影响因子：
3.9
通讯作者：
Huo S
中科院分区：
文献类型：
--
作者：
Vezzu DA;Lu Q;Chen YH;Huo S
筛选了一系列具有不同配位模式和几何构型的环化铂配合物的抗癌活性。发现基于1，3-二（吡啶基）苯的N-[2，3-二甲基吡啶基]-N-配位铂配合物对人肺癌细胞NCI-H522、HCC 827和NCI-H1299以及人前列腺癌细胞RV 1的细胞毒性比顺铂高得多。与此形成鲜明对比的是，基于6-苯基-2，2 ′-联吡啶的C-CN-CN-配位铂配合物对这些癌细胞无效。这种显着的细胞毒性差异显示由N <$C <$N-和C <$N <$N-配位的铂配合物与环化铂配合物中的碳供体的反式效应，这在促进氯配体的解离，创造一个活性结合位点中发挥了至关重要的作用。用电泳和发射滴定法研究了N-氰基-N-配位铂配合物与DNA的结合。荧光显微镜下观察到的细胞摄取结果表明，复合物主要集中在细胞质中。Western blot分析细胞凋亡的可能途径，并观察caspase 7对PARP的激活作用。
A series of cyclometalated platinum complexes with diverse coordination patterns and geometries were screened for their anticancer activity. It was discovered that the NʌCʌN-coordinated platinum complex based on 1,3-di(pyridyl)benzene displayed much higher cytotoxicity against human lung cancer cells NCI-H522, HCC827, and NCI-H1299, and human prostate cancer cell RV1 than cisplatin. In a sharp contrast, the CʌNʌN-coordinated platinum complex based on 6-phenyl-2,2′-bipyridine was ineffective on these cancer cells. This remarkable difference in cytotoxicity displayed by NʌCʌN- and CʌNʌN-coordinated platinum complexes was related to the trans effect of the carbon donor in the cyclometalated platinum complexes, which played a crucial role in facilitating the dissociation of the chloride ligand to create an active binding site. The DNA binding was studied for the NʌCʌN-coordinated platinum complex using electrophoresis and emission titration. The cellular uptake observed by fluorescent microscope showed the complex is largely concentrated in the cytoplasm. The possible pathways for the cell apoptosis was studied by western blot analysis and the activation of PARP via caspase 7 was observed.
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影响因子：
2.6
作者：
Huo, Shouquan;Harris, Caleb F.;Li, Yumin
通讯作者：
Li, Yumin
影响因子：
2.8
作者：
Cárdenas, DJ;Echavarren, AM;de Arellano, MCR
通讯作者：
de Arellano, MCR
通过磺胺嗪调节顺铂细胞毒性。
影响因子：
8.8
作者：
Awasthi, S;Sharma, R;Singhal, S S;Herzog, N K;Chaubey, M;Awasthi, Y C
通讯作者：
Awasthi, Y C
有机金属抗癌化合物。
影响因子：
7.3
作者：
Gasser G;Ott I;Metzler-Nolte N
通讯作者：
Metzler-Nolte N
影响因子：
15
作者：
Melaiye, A;Sun, ZH;Youngs, WJ
通讯作者：
Youngs, WJ