Influence of Ligand and Nuclearity on the Cytotoxicity of Cyclometallated C^N^C Platinum(II) Complexes.
Influence of Ligand and Nuclearity on the Cytotoxicity of Cyclometallated C^N^C Platinum(II) Complexes.
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DOI：
10.1002/chem.202002517
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发表时间：
2020-11-20
期刊：
影响因子：
--
通讯作者：
Pike SJ
中科院分区：
文献类型：
--
作者：
Kergreis A;Lord RM;Pike SJ
合成了一系列环金属化单核和二核铂（II）配合物及其母体有机配体2,6 -二苯基吡啶1 （HC^N^CH）。该化合物库包括[(C^N^C)PtII(L)] （L=二甲亚砜（DMSO） 2和三苯基膦（PPh3） 3）和[((C^N^C)PtII)2(L ‘)](其中L ‘ =N‐杂环（吡嗪（pyr） 4,4,4 ’‐联吡啶（4,4 ’‐联吡啶）5或二膦（1,4‐双（二苯基膦）丁烷（dppb） 6））。对四种癌细胞系和一种正常细胞系进行了细胞毒性评估，结果显示，与单核复合物（2和3）相比，双核复合物的抗增殖活性显著增加（4-6）。复合物6是最有希望的候选者，对癌细胞表现出非常高的选择性，其选择性指数（SI）值为>29.5 （A2780）和>11.2 (A2780cisR)，分别比顺铂高>4倍和>18倍。一项环金属化单核和二核铂（II）复合物库对一系列卵巢癌和乳腺癌细胞系的细胞毒性研究表明，配体类型和核性对其抗增殖活性都很重要。主要候选物是二核铂(II) -膦复合物，对癌细胞表现出非常高的选择性，对顺铂耐药卵巢癌细胞的选择性指数（SI）值为>11.2，比单齿类似物高出>11倍，比顺铂高出>18倍。
A series of cyclometallated mono‐ and di‐nuclear platinum(II) complexes and the parent organic ligand, 2,6‐diphenylpyridine 1 (HC^N^CH), have been synthesized and characterized. This library of compounds includes [(C^N^C)PtII(L)] (L=dimethylsulfoxide (DMSO) 2 and triphenylphosphine (PPh3) 3) and [((C^N^C)PtII)2(L‘)] (where L‘=N‐heterocycles (pyrazine (pyr) 4, 4,4‘‐bipyridine (4,4‘‐bipy) 5 or diphosphine (1,4‐bis(diphenylphosphino)butane (dppb) 6). Their cytotoxicity was assessed against four cancerous cell lines and one normal cell line, with results highlighting significantly increased antiproliferative activity for the dinuclear complexes (4–6), when compared to the mononucleated species (2 and 3). Complex 6 is the most promising candidate, displaying very high selectivity towards cancerous cells, with selectivity index (SI) values >29.5 (A2780) and >11.2 (A2780cisR), and outperforming cisplatin by >4‐fold and >18‐fold, respectively. A study of the cytotoxicity of a library of cyclometallated mono‐ and di‐nuclear platinum(II)‐complexes, against a range of ovarian and breast cancer cell lines, identifies the importance of both ligand type and nuclearity on their antiproliferative activity. The lead candidate, a di‐nuclear platinum(II)‐phosphine complex, exhibits very high selectivity towards cancerous cells, with a selectivity index (SI) value >11.2 against cisplatin‐resistant ovarian cancer cells and outperforming monodentate analogues by >11‐fold and cisplatin by >18‐fold.
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影响因子：
4
作者：
Harper, Benjamin W. J.;Aldrich-Wright, Janice R.
通讯作者：
Aldrich-Wright, Janice R.
影响因子：
3.9
作者：
Harper, Benjamin W. J.;Morris, Thomas T.;Aldrich-Wright, Janice R.
通讯作者：
Aldrich-Wright, Janice R.
DOI：
10.1073/pnas.71.10.3839
发表时间：
1974-01-01
影响因子：
11.1
作者：
JENNETTE, KW;LIPPARD, SJ;BAUER, WR
通讯作者：
BAUER, WR
影响因子：
4.6
作者：
Lai, SW;Chan, MCW;Che, CM
通讯作者：
Che, CM
影响因子：
3
作者：
Alexander, Carlson;Prajith, N. U.;Samy, N. Arockia
通讯作者：
Samy, N. Arockia